697
N. M. Barl et al.
Paper
Synthesis
IR (Diamond-ATR, neat): 2856, 1732, 1456, 1409, 1392, 1376, 1253,
1005, 774 cm–1
Ethyl 2-[1-(tert-Butyldimethylsilyl)-2-methyl-1H-pyrrolo[2,3-
b]pyridin-3-yl]nonanoate (8e)
.
1H NMR (300 MHz, CDCl3): δ = 8.24 (dd, J = 4.6, 1.5 Hz, 1 H), 7.95 (dd,
J = 7.9, 1.6 Hz, 1 H), 7.12 (s, 1 H), 7.00 (dd, J = 7.9, 4.7 Hz, 1 H), 4.21–
4.06 (m, 2 H), 3.75 (t, J = 7.7 Hz, 1 H), 2.15–2.07 (m, 1 H), 1.91–1.82
(m, 1 H), 1.29–1.17 (m, 13 H), 0.90–0.83 (m, 12 H), 0.62 (s, 6 H).
13C NMR (75 MHz, CDCl3): δ = 174.4, 154.3, 142.5, 128.2, 127.1, 121.4,
115.6, 114.3, 60.5, 43.7, 32.5, 31.8, 29.3, 29.1, 27.7, 26.5, 22.6, 19.0,
14.2, 14.1, –4.2.
Prepared according to GP1 from TMPZnCl·LiCl (1.11 M in THF, 1.95
mmol, 1.5 equiv) and ethyl nonanoate (7c; 242 mg, 1.30 mmol, 1.0
equiv) in THF (2 mL) at 25 °C within 10 min. According to GP2, the
thus-obtained zinc reagent 6c was reacted with 3-bromo-1-(tert-bu-
tyldimethylsilyl)-2-methyl-1H-pyrrolo[2,3-b]pyridine (5b; 255 mg,
0.78 mmol, 0.6 equiv), Pd(O2CCF3)2 (7 mg, 2 mol%), and SPhos (16 mg,
4 mol%) at 50 °C for 3 h. Purification of the crude product by flash
chromatography (SiO2, isohexane–Et2O, 40:1) afforded 8e as a color-
less oil; yield: 280 mg (81%).
MS (EI, 70 eV): m/z (%) = 416 (32 [M+]), 360 (23), 359 (61), 344 (29),
343 (100), 331 (21), 201 (24).
IR (Diamond-ATR, neat): 2925, 1733, 1394, 1028, 824, 812, 668 cm–1
.
HRMS (EI): m/z calcd for C24H40N2O2Si: 416.2859; found: 416.2850.
1H NMR (300 MHz, CDCl3): δ = 8.11 (dd, J = 4.6, 1.4 Hz, 1 H), 7.90 (dd,
J = 7.8, 1.4 Hz, 1 H), 6.92 (dd, J = 7.8, 4.7 Hz, 1 H), 4.20–4.04 (m, 2 H),
3.76–3.72 (m, 1 H), 2.22–2.12 (m, 1 H), 1.94–1.80 (m, 1 H), 1.27–1.13
(m, 13 H), 0.90–0.81 (m, 12 H), 0.70 (s, 6 H).
Ethyl 2-[1-(tert-Butyldimethylsilyl)-1H-pyrrolo[2,3-b]pyridin-3-
yl]heptanoate (8c)
Prepared according to GP1 from TMPZnCl·LiCl (0.93 M in THF, 1.95
mmol, 1.5 equiv) and ethyl heptanoate (7d; 203 mg, 1.30 mmol, 1.0
equiv) in THF (2 mL) at 25 °C within 10 min. According to GP2, the
thus-obtained zinc reagent 6d was reacted with 5a (245 mg,
0.79 mmol, 0.6 equiv), Pd(O2CCF3)2 (7 mg, 2 mol%), and SPhos (16 mg,
4 mol%) at 50 °C for 1 h. Purification of the crude product by flash
chromatography (SiO2, isohexane–Et2O, 40:1) afforded 8c as a color-
less oil; yield: 251 mg (82%).
13C NMR (75 MHz, CDCl3): δ = 174.3, 154.8, 140.8, 138.7, 126.3, 121.0,
115.4, 111.4, 60.4, 43.0, 31.7, 31.4, 29.3, 29.1, 27.6, 27.0, 22.6, 20.1,
14.4, 14.2, 14.0, –0.5.
MS (EI, 70 eV): m/z (%) = 430 (7, [M+]), 357 (25), 243 (46), 145 (51), 75
(55), 73 (37), 44 (99), 43 (100).
HRMS (EI): m/z calcd for C25H42N2O2Si: 430.3016; found: 430.3017.
IR (Diamond-ATR, neat): 2857, 1731, 1456, 1392, 1006, 841, 748 cm–1
.
Ethyl 2-[1-(tert-Butyldimethylsilyl)-2-methyl-1H-pyrrolo[2,3-
b]pyridin-3-yl]heptanoate (8f)
1H NMR (300 MHz, CDCl3): δ = 8.24 (dd, J = 4.7, 1.5 Hz, 1 H), 7.95 (dd,
J = 7.9, 1.6 Hz, 1 H), 7.12 (s, 1 H), 7.00 (dd, J = 7.9, 4.7 Hz, 1 H), 4.18–
4.06 (m, 2 H), 3.75 (t, J = 7.7 Hz, 1 H), 2.15–2.08 (m, 1 H), 1.91–1.81
(m, 1 H), 1.29–1.17 (m, 9 H), 0.90–0.82 (m, 12 H), 0.62 (s, 6 H).
13C NMR (75 MHz, CDCl3): δ = 174.4, 154.3, 142.5, 128.2, 127.1, 121.4,
115.6, 114.3, 60.5, 43.7, 32.4, 31.5, 27.3, 26.5, 22.5, 19.0, 14.2, 14.0,
–4.2.
Prepared according to GP1 from TMPZnCl·LiCl (1.11 m in THF, 1.95
mmol, 1.5 equiv) and ethyl heptanoate (7d; 206 mg, 1.30 mmol, 1.0
equiv) in THF (2 mL) at 25 °C within 10 min. According to GP2, the
thus-obtained zinc reagent 6d was reacted with 5b (255 mg,
0.78 mmol, 0.6 equiv), Pd(O2CCF3)2 (7 mg, 2 mol%), and SPhos (16 mg,
4 mol%) at 50 °C for 3 h. Purification of the crude product by flash
chromatography (SiO2, isohexane–Et2O, 40:1) afforded 8f as a color-
less oil; yield: 208 mg (67%).
MS (EI, 70 eV): m/z (%) = 388 (32 [M+]), 331 (62), 315 (100), 201 (36),
201 (41), 131 (48), 75 (28), 73 (76).
IR (Diamond-ATR, neat): 2928, 1717, 1378, 1110, 811, 690 cm–1
.
HRMS (EI): m/z calcd for C22H36N2O2Si: 388.2546; found: 388.2541.
1H NMR (300 MHz, CDCl3): δ = 8.11 (dd, J = 4.6, 1.5 Hz, 1 H), 7.90 (dd,
J = 7.9, 1.5 Hz, 1 H), 6.92 (dd, J = 7.9, 4.7 Hz, 1 H), 4.13–4.04 (m, 2 H),
3.75 (dd, J = 8.4, 7.1 Hz, 1 H), 2.22–2.14 (m, 1 H), 1.93–1.84 (m, 1 H),
1.28–1.18 (m, 8 H), 1.15 (t, J = 7.1 Hz, 3 H), 0.90 (s, 9 H), 0.82 (m, 3 H),
0.70 (s, 6 H).
13C NMR (75 MHz, CDCl3): δ = 174.3, 154.8, 140.8, 138.7, 126.3, 121.0,
115.4, 111.5, 60.4, 43.1, 31.6, 31.3, 27.3, 27.0, 22.5, 20.1, 14.4, 14.2,
14.0, –0.5.
Ethyl 2-[1-(tert-Butyldimethylsilyl)-1H-pyrrolo[2,3-b]pyridin-3-
yl]-3-methylbutanoate (8d)
Prepared according to GP1 from TMPZnCl·LiCl (0.93 M in THF, 1.95
mmol, 1.5 equiv) and ethyl 3-methylbutanoate (7e; 167 mg, 1.30
mmol, 1.0 equiv) in THF (2 mL) at 25 °C within 10 min. According to
GP2, the thus-obtained zinc reagent 6e was reacted with 5a (245 mg,
0.79 mmol, 0.6 equiv), Pd(O2CCF3)2 (7 mg, 2 mol%), and SPhos (16 mg,
4 mol%) at 50 °C for 1 h. Purification of the crude product by flash
chromatography (SiO2, isohexane–Et2O, 40:1) afforded 8d as a color-
less oil; yield: 183 mg (64%).
MS (EI, 70 eV): m/z (%) = 402 (22, [M+]), 346 (26), 345 (26), 331 (23),
330 (26), 329 (100), 273 (27).
HRMS (EI): m/z calcd for C23H38N2O2Si: 402.2703; found: 402.2693.
IR (Diamond-ATR, neat): 2929, 1731, 1408, 1005, 823, 810, 668 cm–1
.
Ethyl 2-[1-(tert-Butyldimethylsilyl)-5-chloro-1H-pyrrolo[2,3-
b]pyridin-3-yl)-3-methylbutanoate (8g)
1H NMR (300 MHz, CDCl3): δ = 8.24 (dd, J = 4.6, 1.5 Hz, 1 H), 8.00 (dd,
J = 7.9, 1.6 Hz, 1 H), 7.17 (s, 1 H), 7.00 (dd, J = 7.9, 4.7 Hz, 1 H), 4.21–
4.05 (m, 2 H), 3.40 (d, J = 10.0 Hz, 1 H), 2.50–2.40 (m, 1 H), 1.21 (t, J =
7.1 Hz, 3 H), 1.05 (d, J = 6.5 Hz, 3 H), 0.89 (s, 9 H), 0.77 (d, J = 6.7 Hz, 3
H), 0.63 (s, 6 H).
13C NMR (75 MHz, CDCl3): δ = 174.0, 154.2, 142.5, 129.1, 127.4, 121.7,
115.6, 113.3, 60.4, 51.9, 31.3, 26.5, 21.4, 20.5, 19.0, 14.2, –4.2.
Prepared according to GP1 from TMPZnCl·LiCl (1.11 m in THF, 1.95
mmol, 1.5 equiv) and ethyl 3-methylbutanoate (7e; 169 mg, 1.3
mmol, 1.0 equiv) in THF (2 mL) at 25 °C within 10 min. According to
GP2, the thus-obtained zinc reagent 6e was reacted with 3-bromo-1-
(tert-butyldimethylsilyl)-5-chloro-1H-pyrrolo[2,3-b]pyridine
(5c;
277 mg, 0.8 mmol, 0.6 equiv), Pd(O2CCF3)2 (7 mg, 2 mol%), and SPhos
(16 mg, 4 mol%) at 50 °C for 1 h. Purification of the crude product by
flash chromatography (SiO2, isohexane–Et2O, 100:1 → 60:1) afforded
8g as a colorless oil; yield: 140 mg (44%).
MS (EI, 70 eV): m/z (%) = 360 (31, [M+]), 38 (26), 317 (100), 303 (43),
287 (44), 261 (26), 73 (66).
HRMS (EI): m/z calcd for C20H32N2O2Si: 360.2233; found: 360.2227.
IR (Diamond-ATR, neat): 2929, 1730, 1395, 1117, 866, 667 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 692–700