Diisopropylethylamine → N-[(4S)-6'-Bromo-3-methyl-2,5-dioxo-1',3'-dihydrospiro[imidazolidine-4,2'-inden]-5'-yl]-2-(2-oxo-3-pyridin-2-yl-2,3-dihydro-1H-benzimidazol-1-yl)acetamide

HRID 656417Notes

Reaction equation

HRID 656417 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Br:11])[CH2:7][C@:6]1([C:15](=[O:16])[NH:14][C:13](=[O:17])[N:12]1[CH3:18])[CH2:5]2.[O:19]=[C:20]1[N:24]([CH2:25][C:26](O)=[O:27])[C:23]2[CH:29]=[CH:30][CH:31]=[CH:32][C:22]=2[N:21]1[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=1.C(N(CC)C(C)C)(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:11][C:10]1[CH:9]=[C:8]2[C:4]([CH2:5][C@@:6]3([C:15](=[O:16])[NH:14][C:13](=[O:17])[N:12]3[CH3:18])[CH2:7]2)=[CH:3][C:2]=1[NH:1][C:26](=[O:27])[CH2:25][N:24]1[C:23]2[CH:29]=[CH:30][CH:31]=[CH:32][C:22]=2[N:21]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)[C:20]1=[O:19]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOP2×HCID 18449368(2-Oxo-3-pyridin-2-yl-2,3-dihydro-1H-benzimidazol-1-yl)acetic acid2×HCID 57774228(S)-5'-amino-6'-bromo-3-methyl-spiro[imidazolidine-4,2'-indane]-2,5-dione2×

Product 1

HCID 68996253N-[(4S)-6'-Bromo-3-methyl-2,5-dioxo-1',3'-dihydrospiro[imidazolidine-4,2'-inden]-5'-yl]-2-(2-oxo-3-pyridin-2-yl-2,3-dihydro-1H-benzimidazol-1-yl)acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred mixture of (S)-5′-amino-6′-bromo-3-methyl-spiro[imidazolidine-4,2′-indane]-2,5-dione (50 mg, 0.161 mmol, described in Intermediate 18) and (2-oxo-3-pyridin-2-yl-2,3-dihydro-1H-benzimidazol-1-yl)acetic acid (52 mg, 0.193 mmol, described in Intermediate 16) in DMF (1 mL) were added N,N-diisopropylethylamine (0.028 mL, 0.161 mmol), followed by PyBOP (126 mg, 0.242 mmol). The reaction mixture was heated to 40° C. for 5 h, then PyBOP (126 mg, 0.242 mmol) was added and heating was continued for 18 h. The cooled mixture was purified 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. The pure, product-containing fractions were combined and concentrated to give the title compound. MS: m/z=563 (M+1).

Workup

  1. temperatureheating
  2. customThe cooled mixture was purified by HPLC
  3. washeluting with a gradient of H2O
  4. additionThe pure, product-containing fractions
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-008dfba5b44c4512a77cc8c0bf0294c3
Source dataset
uspto-grants-2011_12
Patent number
US08071771B2

Reaction notes

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