HCID 54502192, compound → HCID 18463938, compound

HRID 2231075Notes

Reaction equation

HRID 2231075 reaction equation
C([O:5][C:6](=[O:37])[CH2:7][N:8]1[C:14](=[O:15])[CH:13]([NH:16][C:17]([C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21][N:20]=2)=[O:18])[CH2:12][CH2:11][C:10](=[O:29])[N:9]1[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)(C)(C)C>FC(F)(F)C(O)=O.ClCCl>[CH2:30]([N:9]1[C:10](=[O:29])[CH2:11][CH2:12][CH:13]([NH:16][C:17]([C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21][N:20]=2)=[O:18])[C:14](=[O:15])[N:8]1[CH2:7][C:6]([OH:37])=[O:5])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

4

Reactant 1

HCID 54502192HCID 54502192, compound

Product 1

HCID 18463938HCID 18463938, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

{2-Benzyl-6-[(isoquinoline-1-carbonyl)-amino]-3,7-dioxo-[1,2]diazepan-1-yl}-acetic acid tert-butyl ester (7a) (115 mg, 0.23 mmol) was stirred in 20% of trifluoroacetic acid (TFA) in dichloromethane (2 mL) overnight. The solution was evaporated to afford {2-benzyl-6-[(isoquinoline-1-carbonyl)-amino]-3,7-dioxo-[1,2]diazepan-1-yl}-acetic acid (8a). 1H-NMR (500 MHz, CDCl3) δ 2.05-2.11 (m, 1H), 2,45-2.50 (m, 1H), 2.72-2.83 (m, 1H), 3.45-3.54 (m, 1H), 4.01-4.06 (d, 1H), 4.59-4.63 (d, 1H), 4.70-4.82 (m, 2H), 4.93-4.98 (d, 1H), 7.28-7.42 (m, 5H), 7.80-8.10 (m, 4H), 8.40-8.52 (m, 2H), 8.85 (d, 1H). The acid (8a) was dissolved in dichloromethane (2 mL) followed by addition of HOBT (77 mg, 0.57 mmol) and EDC (110 mg, 0.57 mmol) and stirred for 30 min. A solution of (2-benzyloxy-5-oxo-tetrahydro-furan-3-yl)-carbamic acid allyl ester (9, anti diastereomer) (166 mg, 0.57 mmol) in dichloromethane/DMF (3/1 mL), charged with 1,3-dimethylbarbituric acid (DMBA) (90 mg, 0.57 mmol) and Pd(PPh3)4 (66 mg, 0.057 mmol) for 30 min, was added and the resulting mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (50 mL×3), dried over Na2SO4, filtered and evaporated to give a pale yellow solid, that was purified by flash chromatography using dichloromethane/methanol (99.5/0.5 to 98.5/1.5) to afford 97.5 mg (67% yield) of the title compound. 1H-NMR (500 MHz, CDCl3) δ 2.03-2.13 (m, 1H), 2.40-2.43 (d, 1H), 2.55-2.60 (m, 1H), 2.83-2.92 (m, 1H), 3.04-3.10 (q, 1H), 3.28-3.38 (m, 1H), 4.08-4.11 (d, 1H), 4.20-4.24 (d, 1H), 4.38-4.41 (m, 1H), 4.67-4.70 (d, 1H), 4.78-4.87 (m, 2H), 4.91-5.02 (m, 2H), 5.36 (s, 1H), 6.05 (d, 1H), 7.20-7.38 (m, 10H), 7.68-7.78 (m, 2H), 7.80-7.88 (m, 2H), 8.48 (d, 1H), 8.70 (d, 1H), 9.49 (d, 1H). Analytical HPLC: 12.53 min. LC-MS (ES+): m/e=636 (M+H+).

Workup

  1. customThe solution was evaporated

Sources & evidence

ORD record
ord-42b49bedf6524c1f97e7228f37dc302e
Source dataset
uspto-grants-2002_07
Patent number
US06426413B1

Reaction notes

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