alanine methyl ester hydrochloride (156 mg, 1.12 mmol) was
chromatographed using diethyl ether–hexane 9 : 1 as the eluent
to give the ester 2c (360 mg, 91%), mp 132.4–134.1 ЊC, Rf 0.56
(diethyl ether–hexane 9 : 1) (Found: C, 64.65; H, 6.21; N, 15.68.
C19H22N4O3 requires C, 64.39; H, 6.26; N, 15.81%).
reaction of 2b (247 mg, 0.73 mmol) was chromatographed with
diethyl ether–hexane 6 : 4 as the eluent; the solid material thus
obtained was recrystallised from ethyl acetate–hexane to give
ester 3b (288 mg, 90%), mp 114.8–116.0 ЊC, Rf 0.40 (diethyl
ether–hexane 6 : 4) (Found: C, 62.61; H, 6.38; N, 12.55.
C23H28N4O5 requires C, 62.71; H, 6.41; N, 12.72%).
N-{3-[(N,N-Dimethylaminophenyl)-4Ј-diazenyl]benzoyl}valine
methyl ester 2d. The product of reaction of 1 with valine methyl
ester hydrochloride (188 mg, 1.12 mmol) was chromatographed
using diethyl ether–hexane 9 : 1 as the eluent to give the ester 2d
(346 mg, 81%), mp 114.3–115.9 ЊC, Rf 0.70 (diethyl ether–
hexane 9 : 1) (Found: C, 65.74; H, 6.88; N, 14.74. C21H26N4O3
requires C, 65.95; H, 6.85; N, 14.65%).
N-{3-[(N,N-Dimethylaminophenyl)-4Ј-diazenyl]benzoyl}-
N-tert-butyloxycarbonylalanine methyl ester 3c. The product of
reaction of 2c (50 mg, 0.14 mmol) was chromatographed with
diethyl ether–light petroleum 9 : 1 as the eluent to give ester 3c
(63 mg, 99%), mp 101.8–103.4 ЊC, Rf 0.74 (diethyl ether–hexane
8 : 2) (Found: C, 63.52; H, 6.55; N, 12.21. C24H30N4O5 requires
C, 63.42; H, 6.65; N, 12.33%).
N-{3-[(N,N-Dimethylaminophenyl)-4Ј-diazenyl]benzoyl}-
isoleucine methyl ester 2e. The product of reaction of 1 with
isoleucine methyl ester hydrochloride (203 mg, 1.12 mmol) was
chromatographed using diethyl ether–hexane 9 : 1 as the eluent
to give the ester 2e (351 mg, 79%), mp 117.3–118.1 ЊC, Rf 0.78
(diethyl ether–hexane 9 : 1) (Found: C, 66.68; H, 7.16; N, 14.21.
C22H28N4O3 requires C, 66.64; H, 7.12; N, 14.13%).
N-{3-[(N,N-Dimethylaminophenyl)-4Ј-diazenyl]benzoyl}-
N-tert-butyloxycarbonylvaline methyl ester 3d. The product of
reaction of 2d (189 mg, 0.50 mmol) was chromatographed using
diethyl ether–hexane 2 : 8 as the eluent to give ester 3d (203 mg,
85%), mp 147.6–149.0 ЊC, Rf 0.62 (diethyl ether–hexane 6 : 4)
(Found: C, 64.94; H, 6.82; N, 11.63. C26H34N6O5 requires C,
64.71; H, 7.10; N, 11.61%).
N-{3-[(N,N-Dimethylaminophenyl)-4Ј-diazenyl]benzoyl}l-
eucine methyl ester 2f. The product of reaction of 1 with leucine
methyl ester hydrochloride (162 mg, 1.12 mmol) was chromato-
graphed using diethyl ether–light petroleum 9.5 : 0.5 as the
eluent to give the ester 2f (260 mg, 59%), mp 136.4–137.5 ЊC, Rf
0.71 (diethyl ether–light petroleum 9.5 : 0.5) (Found: C, 66.69;
H, 7.11; N, 14.10. C22H28N4O3 requires C, 66.64; H, 7.12; N,
14.13%).
N-{3-[(N,N-Dimethylaminophenyl)-4Ј-diazenyl]benzoyl}-
N-tert-butyloxycarbonylisoleucine methyl ester 3e. The product
of reaction of 2e (220 mg, 0.56 mmol) was chromatographed
with diethyl ether–hexane 4 : 6 as the eluent to give ester 3e (154
mg, 56%), mp 89.2–91.0 ЊC, Rf 0.56 (diethyl ether–hexane 4 : 6)
(Found: C, 65.20; H, 7.39; N, 11.04. C27H36N4O5 requires C,
65.30; H, 7.31; N, 11.28%).
N-{3-[(N,N-Dimethylaminophenyl)-4Ј-diazenyl]benzoyl}-
N-tert-butyloxycarbonylleucine methyl ester 3f. The product of
reaction of 2f (130 mg, 0.33 mmol) was chromatographed with
ethyl acetate–hexane 6 : 4 as the eluent to give ester 3f (161 mg,
99%), Rf 0.59 (diethyl ether–hexane 6 : 4); m/z (EI) 496.268479
(Mϩ. C27H36N4O5 requires 496.268571).
N-{3-[(N,N-Dimethylaminophenyl)-4Ј-diazenyl]benzoyl}-
methionine methyl ester 2g. The product of reaction of 1 with
methionine methyl ester hydrochloride (223 mg, 1.12 mmol)
was chromatographed using diethyl ether–light petroleum
9.5 : 0.5 as the eluent to give the ester 2g (323 mg, 70%), mp
120.5–121.3 ЊC, Rf 0.68 (diethyl ether–light petroleum 9.5 : 0.5)
(Found: C, 60.81; H, 6.32; N, 13.56; S, 7.53. C21H26N4O3S
requires C, 60.84; H, 6.32; N, 13.52; S, 7.74%).
N-{3-[(N,N-Dimethylaminophenyl)-4Ј-diazenyl]benzoyl}-
N-tert-butyloxycarbonylmethionine methyl ester 3g. The prod-
uct of reaction of 2g (210 mg, 0.51 mmol) was chromato-
graphed with diethyl ether–hexane 3 : 7 as the eluent to give
ester 3g (155 mg, 60%), Rf 0.47 (diethyl ether–hexane 6 : 4); m/z
(EI) 514.225675 (Mϩ. C26H34N4O5S requires 514.224992).
N-{3-[(N,N-Dimethylaminophenyl)-4Ј-diazenyl]benzoyl}-
phenylalanine ethyl ester 2h. The product of reaction of 1 with
phenylalanine ethyl ester hydrochloride (257 mg, 1.12 mmol)
was chromatographed using chloroform–methanol 6 : 1 as the
eluent to give the ester 2h (385 mg, 77%), mp 152.7–153.8 ЊC, Rf
0.70 (diethyl ether–light petroleum 9.5 : 0.5) (Found: C, 70.28;
H, 6.37; N, 12.68. C26H28N4O3 requires C, 70.25; H, 6.35; N,
12.61%).
N-{3-[(N,N-Dimethylaminophenyl)-4Ј-diazenyl]benzoyl}-
N-tert-butyloxycarbonylphenylalanine ethyl ester 3h. The prod-
uct of reaction of 2h (62.6 mg, 0.14 mmol) was chromato-
graphed with diethyl ether–hexane 1 : 1 as the eluent to give
ester 3h (76 mg, 99%), Rf 0.40 (diethyl ether–hexane 1 : 1)
(Found: C, 68.48; H, 6.75; N, 9.88. C31H36N4O5 requires C,
68.36; H, 6.66; N, 10.29%).
N-{3-[(N,N-Dimethylaminophenyl)-4Ј-diazenyl]benzoyl}-
phenylalanylvaline tert-butyl ester 2i. The product of reaction of
1 with phenylalanyl-valine tert-butyl ester (161 mg, 0.60 mmol)
was chromatographed using chloroform–methanol (mixtures
of increasing polarity) as the eluent to give ester 2i (267 mg,
78%), mp 164.8–166.9 ЊC, Rf 0.71 (ethyl acetate–hexane 6 : 4)
(Found C, 69.02; H, 7.00; N, 12.30. C33H41N5O4 requires C,
69.33; H, 7.23; N 12.25%).
General method of aminolysis of the coloured amino acid esters
The coloured substrates 3b–h in acetonitrile were treated with a
given amount of DEAEA for one or more days according to
the procedure of Grehn et al.11 The products were purified by
flash chromatography to give the corresponding Boc-amino
acid esters 4b–h together with the transamination product 5.
General method for preparation of Boc-acylamides
To a solution of the required substrate in dry acetonitrile (47
mmol dmϪ3) 0.3 eq. of DMAP was added followed by 3.6 eq. of
di-tert-butyl pyrocarbonate under rapid stirring overnight at
room temperature, the reaction being monitored by TLC.
Evaporation under reduced pressure followed by dry chrom-
atography on silica gel and recrystallisation gave the required
Boc-acylamide as an orange residue.
N-tert-Butyloxycarbonylglycine methyl ester 4b, by aminolysis
of 3b. The product of a 1 day reaction of 3b (100 mg, 0.23
mmol) with DEAEA (0.16 cm3, 0.11 mmol) was chromato-
graphed with diethyl ether–hexane 4 : 6 as the eluent to give
ester 4b (24 mg, 56%), Rf 0.54 (diethyl ether–hexane 6 : 1)
(Found: C, 50.57; H, 7.82; N, 7.09. C8H15NO4 requires C, 50.78;
H, 7.99; N, 7.40%).
N-{3-[(N,N-Dimethylaminophenyl)-4Ј-diazenyl]benzoyl}-
N-tert-butyloxycarbonylglycine methyl ester 3b. The product of
N-tert-Butyloxycarbonylalanine methyl ester 4c, by aminolysis
of 3c. The product of a 2 day reaction of 3c (75 mg, 0.17 mmol)
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 4 8 0 – 1 4 8 5
1483