Triethylamine → 3-Cyclopentyl-1-methyl-2-pyrazin-2-yl-1h-indole-6-carboxylic acid{1-[5-((e)-2-carbamoylethenyl)-1-methyl-1h-benzoimidazol-2-yl]cyclobutyl}amide

HRID 1360632Notes

Reaction equation

HRID 1360632 reaction equation
[CH:1]1([C:6]2[C:14]3[C:9](=[CH:10][C:11]([C:15]([NH:17][C:18]4([C:22]5[N:26]([CH3:27])[C:25]6[CH:28]=[CH:29][C:30](/[CH:32]=[CH:33]/[C:34](O)=[O:35])=[CH:31][C:24]=6[N:23]=5)[CH2:21][CH2:20][CH2:19]4)=[O:16])=[CH:12][CH:13]=3)[N:8]([CH3:37])[C:7]=2[C:38]2[CH:43]=[N:42][CH:41]=[CH:40][N:39]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C[N:45](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(=O)([O-])O.[NH4+].CCN(CC)CC>CS(C)=O.C(O)(=O)C>[C:34](/[CH:33]=[CH:32]/[C:30]1[CH:29]=[CH:28][C:25]2[N:26]([CH3:27])[C:22]([C:18]3([NH:17][C:15]([C:11]4[CH:10]=[C:9]5[C:14]([C:6]([CH:1]6[CH2:5][CH2:4][CH2:3][CH2:2]6)=[C:7]([C:38]6[CH:43]=[N:42][CH:41]=[CH:40][N:39]=6)[N:8]5[CH3:37])=[CH:13][CH:12]=4)=[O:16])[CH2:21][CH2:20][CH2:19]3)=[N:23][C:24]=2[CH:31]=1)(=[O:35])[NH2:45]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 14013Ammonium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 57835349(E)-3-(2-{1-[(3-Cyclopentyl-1-methyl-2-pyrazin-2-yl-1H-indole-6-carbonyl)amino]cyclobutyl}-1-methyl-1H-benzimidazol-5-yl)acrylic acid

Product 1

HCID 578352803-Cyclopentyl-1-methyl-2-pyrazin-2-yl-1h-indole-6-carboxylic acid{1-[5-((e)-2-carbamoylethenyl)-1-methyl-1h-benzoimidazol-2-yl]cyclobutyl}amideYield 34%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of (E)-3-(2-{1-[(3-cyclopentyl-1-methyl-2-pyrazin-2-yl-1H-indole-6-carbonyl)amino]cyclobutyl}-1-methyl-1H-benzimidazol-5-yl)acrylic acid 5-2 (compound 4003, Table 4; 60 mg, 0.087 mmol), TBTU (68 mg, 0.18 mmol), ammonium hydrogen carbonate (20 mg, 0.26 mmol) and Et3N (36 μL, 0.26 mmol) in DMSO (3 mL) was stirred at RT for 3 h. The reaction mixture was neutralized with the addition of a few drops of acetic acid, and purified on a reversed phase C18, semi-preparative HPLC column (using a solvent gradient from 5% to 100% MeCN in H2O (all solvents contain 0.1% trifluoroacetic acid)) to isolate the inhibitor 3-cyclopentyl-1-methyl-2-pyrazin-2-yl-1H-indole-6-carboxylic acid {1-[5-((E)-2-carbamoylethenyl)-1-methyl-1H-benzoimidazol-2-yl]cyclobutyl}amide 5-3 (compound 1005, Table 1) as a pale yellow amorphous solid in >95% homogeneity (17 mg, 34% yield).

Workup

  1. custompurified on a reversed phase C18, semi-preparative HPLC column (

Sources & evidence

ORD record
ord-03457b84977f4f20bb901a71c2b63181
Source dataset
uspto-grants-2011_02
Patent number
US07879851B2

Reaction notes

Loading…