1,2-Dichloroethane → (s)-7-Chloro-2-neopentyl-4-(2-oxo-2-(4-(5-oxo-4,5-dihydro-1h-pyrrolo[3,2-b]pyridin-6-yl)piperidin-1-yl)ethyl)-1,2,4,5-tetrahydroazepino[3,4-e]indol-3(8h)-one

HRID 2378995Notes

Reaction equation

HRID 2378995 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[C:12](=[O:13])[NH:11][C:10]3[CH:14]=[CH:15][NH:16][C:9]=3[CH:8]=2)[CH2:3][CH2:2]1.[Cl:17][C:18]1[CH:19]=[C:20]2[CH2:31][C@@H:30]([CH2:32][C:33](O)=[O:34])[C:29](=[O:36])[N:28]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:27][C:21]2=[C:22]2[C:26]=1[NH:25][CH:24]=[CH:23]2.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[Cl:17][C:18]1[CH:19]=[C:20]2[CH2:31][C@@H:30]([CH2:32][C:33](=[O:34])[N:1]3[CH2:2][CH2:3][CH:4]([C:7]4[C:12](=[O:13])[NH:11][C:10]5[CH:14]=[CH:15][NH:16][C:9]=5[CH:8]=4)[CH2:5][CH2:6]3)[C:29](=[O:36])[N:28]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:27][C:21]2=[C:22]2[C:26]=1[NH:25][CH:24]=[CH:23]2

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 590063956-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-5(4H)-oneHCID 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 23658028(s)-7-Chloro-2-neopentyl-4-(2-oxo-2-(4-(5-oxo-4,5-dihydro-1h-pyrrolo[3,2-b]pyridin-6-yl)piperidin-1-yl)ethyl)-1,2,4,5-tetrahydroazepino[3,4-e]indol-3(8h)-oneYield 16.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 6-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-5(4H)-one (60.0 mg, 0.276 mmol) 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), DMF (2.0 ml) at rt, followed by diisopropylethylamine (0.192 ml, 1.10 mmol). The resulting mixture was stirred at rt over night, partial of the solvent was removed under N2, and the residue was purified on reverse phase PrepHPLC to afford the expected products(25.2 mg, 16%), (S)-7-chloro-2-neopentyl-4-(2-oxo-2-(4-(5-oxo-4,5-dihydro-1H-pyrrolo [3,2-b]pyridin-6-yl)piperidin-1-yl)ethyl)-1,2,4,5-tetrahydroazepino [3,4-e]indol-3 (8H)-one, as a tan solid. 1H-NMR (400 MHz, MeOD) d 0.79 (d, J=5.29 Hz, 11H) 1.52-1.62 (m, 1H) 1.81 (s, 1H) 2.38-2.49 (m, 1H) 2.75 (s, 1H) 3.01 (d, J=13.35 Hz, 1H) 3.09-3.21 (m, 4H) 3.66 (d, J=13.85 Hz, 1H) 3.96 (s, 3H) 3.99-4.06 (m, 1H) 4.24 (s, 1H) 4.65 (d, J=17.37 Hz, 2H) 5.46-5.55 (m, 1H) 6.27 (dd, J=5.29, 3.02 Hz, 1H) 7.22 (s, 1H) 7.36 (dd, J=7.81, 3.02 Hz, 1H) 8.24 (s, 1H); Mass spec 562.48 (MH+) calc for C31H36ClN5O3 561.25.

Workup

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

Sources & evidence

ORD record
ord-374b439b8d5b4a9cbdb4b0614785c14d
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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