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 2378996Notes

Reaction equation

HRID 2378996 reaction equation
[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

Participants

7

Reactant 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

Product 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)-oneYield 76.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

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

Sources & evidence

ORD record
ord-b6ce1d39d5f14a1688f66074c813f84c
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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