1,2-Dichloroethane → (S)-7-chloro-4-(2-(4-(6-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-hydroxypiperidin-1-yl)-2-oxoethyl)-2-neopentyl-1,2,4,5-tetrahydroazepino[3,4-e]indol-3(8H)-one

HRID 2378996노트

반응식

HRID 2378996 반응식
[Cl:1][C:2]1[N:7]=[C:6]2[NH:8][CH:9]=[CH:10][C:5]2=[C:4]([C:11]2([OH:17])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[CH:3]=1.[Cl:18][C:19]1[CH:20]=[C:21]2[CH2:32][C@@H:31]([CH2:33][C:34](O)=[O:35])[C:30](=[O:37])[N:29]([CH2:38][C:39]([CH3:42])([CH3:41])[CH3:40])[CH2:28][C:22]2=[C:23]2[C:27]=1[NH:26][CH:25]=[CH:24]2.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[Cl:18][C:19]1[CH:20]=[C:21]2[CH2:32][C@@H:31]([CH2:33][C:34]([N:14]3[CH2:13][CH2:12][C:11]([C:4]4[CH:3]=[C:2]([Cl:1])[N:7]=[C:6]5[NH:8][CH:9]=[CH:10][C:5]=45)([OH:17])[CH2:16][CH2:15]3)=[O:35])[C:30](=[O:37])[N:29]([CH2:38][C:39]([CH3:42])([CH3:41])[CH3:40])[CH2:28][C:22]2=[C:23]2[C:27]=1[NH:26][CH:25]=[CH:24]2

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 590063354-(6-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-4-olHCID 68892930(S)-2-(7-chloro-2-neopentyl-3-oxo-1,2,3,4,5,8-hexahydroazepino[3,4-e]indol-4-yl)acetic acid

생성물 1

HCID 23657997(S)-7-chloro-4-(2-(4-(6-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-hydroxypiperidin-1-yl)-2-oxoethyl)-2-neopentyl-1,2,4,5-tetrahydroazepino[3,4-e]indol-3(8H)-one수율 76.5%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To 4-(6-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-4-ol (69 mg, 0.304 mmol) in DMF (2 mL) was added (S)-2-(7-chloro-2-neopentyl-3-oxo-1,2,3,4,5,8-hexahydroazepino[3,4-e]indol-4-yl)acetic acid (100 mg, 0.276 mmol), EDC (58.3 mg, 0.304 mmol), HOBT (41.0 mg, 0.304 mmol), at rt, followed by diisopropylethylamine (0.192 ml, 1.10 mmol). The mixture was stirred at rt over night, partial of the solvent was removed under N2, the residue was purified on reverse phase PrepHPLC to afford the expected product, (S)-7-chloro-4-(2-(4-(6-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-hydroxypiperidin-1-yl)-2-oxoethyl)-2-neopentyl-1,2,4,5-tetrahydroazepino[3,4-e]indol-3(8H)-one (126 mg, 57%) as a tan solid. 1H-NMR (400 MHz, MeOD) δ ppm 0.78-0.84 (m, 11H) 1.73 (s, 1H) 1.76-1.83 (m, 1H) 2.25-2.36 (m, 2H) 2.66-2.76 (m, 1H) 3.03 (d, J=13.35 Hz, 1H) 3.09-3.20 (m, 4H) 3.62-3.73 (m, 2H) 4.08 (d, J=12.84 Hz, 2H) 4.51 (d, J=10.83 Hz, 1H) 4.65 (d, J=17.12 Hz, 1H) 5.51 (d, J=17.12 Hz, 1H) 6.99 (d, J=3.53 Hz, 1H) 7.20-7.24 (m, 2H) 7.26-7.29 (m, 2H) 8.24 (s, 1H); Mass spec. 596.47 (MH+) calc. for C31H35Cl2N5O3 595.21.

후처리

  1. customat rt
  2. customwas removed under N2
  3. customthe residue was purified on reverse phase PrepHPLC

출처 및 근거

ORD 기록
ord-b6ce1d39d5f14a1688f66074c813f84c
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07470680B2

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