1,2-Dichloroethane → tert-butyl((5-((6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamido)methyl)-6-methoxy-4-methylpyridin-2-yl)methyl)carbamate

HRID 1476970Notes

Reaction equation

HRID 1476970 reaction equation
[C:1]([O:5][C:6](=[O:20])[NH:7][CH2:8][C:9]1[CH:14]=[C:13]([CH3:15])[C:12]([CH2:16][NH2:17])=[C:11]([O:18][CH3:19])[N:10]=1)([CH3:4])([CH3:3])[CH3:2].[Br:21][C:22]1[CH:23]=[C:24]([C:35](O)=[O:36])[C:25]2[C:26]([CH3:34])=[CH:27][N:28]([CH:31]([CH3:33])[CH3:32])[C:29]=2[CH:30]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>ClCCl.CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6](=[O:20])[NH:7][CH2:8][C:9]1[CH:14]=[C:13]([CH3:15])[C:12]([CH2:16][NH:17][C:35]([C:24]2[C:25]3[C:26]([CH3:34])=[CH:27][N:28]([CH:31]([CH3:32])[CH3:33])[C:29]=3[CH:30]=[C:22]([Br:21])[CH:23]=2)=[O:36])=[C:11]([O:18][CH3:19])[N:10]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 181649HOAtHCID 674686786-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylic acidHCID 67951653Tert-butyl ((5-(aminomethyl)-6-methoxy-4-methylpyridin-2-yl)methyl)carbamate

Product 1

HCID 68210118tert-butyl((5-((6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamido)methyl)-6-methoxy-4-methylpyridin-2-yl)methyl)carbamateYield 98%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of tert-butyl((5-(aminomethyl)-6-methoxy-4-methylpyridin-2-yl)methyl)carbamate (0.55 g, 1.955 mmol), 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylic acid (0.63 g, 2.127 mmol), and HOAt (0.27 g, 1.984 mmol) in Dichloromethane (20 mL) and DMF (5 mL) was added EDC free base (0.34 g, 2.190 mmol). The reaction was stirred at RT for 2 hr then evaporated to dryness under vacuum. The remaining was purified by silica gel chromatography (Analogix, SF25-60 g, 0 to 40% EtOAc in hexanes) to give the product tert-butyl((5-((6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamido)methyl)-6-methoxy-4-methylpyridin-2-yl)methyl)carbamate (1.07 g, 1.912 mmol, 98% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=8.47 (t, J=4.8 Hz, 1H), 7.76 (d, J=1.8 Hz, 1H), 7.35 (t, 1H), 7.33 (d, J=1.0 Hz, 1H), 6.99 (d, J=1.5 Hz, 1H), 6.67 (s, 1H), 4.74 (quin, J=6.6 Hz, 1H), 4.44 (d, J=4.8 Hz, 2H), 4.08 (d, J=6.3 Hz, 2H), 3.85 (s, 3H), 2.37 (s, 3H), 2.10 (s, 3H), 1.41 (s, 9H), 1.38 (d, J=6.6 Hz, 6H). MS(ES)+m/e 559.3 [M+H]+.

Workup

  1. customthen evaporated to dryness under vacuum
  2. customThe remaining was purified by silica gel chromatography (Analogix

Sources & evidence

ORD record
ord-763d62163ec64e568e34f1f60dba770e
Source dataset
uspto-grants-2016_08
Patent number
US09402836B2

Reaction notes

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