Diisopropylethylamine → 6'-Chloro-3-methyl-5'-{[2-(2-oxo-3-pyridin-2-yl-2,3-dihydro-1H-benzimidazol-1-yl)acetyl]amino}-spiro[imidazolidine-4,2'-indane]-2,5-dione

HRID 1270410Notes

Reaction equation

HRID 1270410 reaction equation
[O:1]=[C:2]1[N:6]([CH2:7][C:8]([OH:10])=O)[C:5]2[CH:11]=[CH:12][CH:13]=[CH:14][C:4]=2[N:3]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1.[NH2:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][C:30]=1[Cl:31])[CH2:27][C:26]1([C:35](=[O:36])[NH:34][C:33](=[O:37])[N:32]1[CH3:38])[CH2:25]2.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[Cl:31][C:30]1[CH:29]=[C:28]2[C:24]([CH2:25][C:26]3([C:35](=[O:36])[NH:34][C:33](=[O:37])[N:32]3[CH3:38])[CH2:27]2)=[CH:23][C:22]=1[NH:21][C:8](=[O:10])[CH2:7][N:6]1[C:5]2[CH:11]=[CH:12][CH:13]=[CH:14][C:4]=2[N:3]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[C:2]1=[O:1]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 18449368(2-Oxo-3-pyridin-2-yl-2,3-dihydro-1H-benzimidazol-1-yl)acetic acid2×HCID 184493935'-Amino-6'-chloro-3-methyl-spiro[imidazolidine-4,2'-indane]-2,5-dione

Product 1

HCID 184493976'-Chloro-3-methyl-5'-{[2-(2-oxo-3-pyridin-2-yl-2,3-dihydro-1H-benzimidazol-1-yl)acetyl]amino}-spiro[imidazolidine-4,2'-indane]-2,5-dione

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (2-oxo-3-pyridin-2-yl-2,3-dihydro-1H-benzimidazol-1-yl)acetic acid (57 mg, 0.211 mmol, described in Intermediate 4), 5′-amino-6′-chloro-3-methyl-spiro[imidazolidine-4,2′-indane]-2,5-dione, enantiomer B (51 mg, 0.192 mmol, described in Intermediate 48), PyBOP (120 mg, 0.230 mmol), and N,N-diisopropylethylamine (0.033 mL, 0.192 mmol) was stirred in DMF (1 mL) at 50° C. for 18 h. The crude mixture was purified directly by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. Lyophilization provided the title compound as a white solid. MS: m/z=517 (M+1). HRMS: m/z=517.1383; calculated m/z=517.1386 for C26H22ClN6O4.

Workup

  1. customThe crude mixture was purified directly by HPLC
  2. washeluting with a gradient of H2O

Sources & evidence

ORD record
ord-af2b27a3d4544404bb14545f97340408
Source dataset
uspto-grants-2007_04
Patent number
US07202251B2

Reaction notes

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