Triethylamine → 2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methyl-N-[1-[3'-({[(1-methylethyl)amino]carbonyl}amino)-4-biphenylyl]-2-(4-morpholinyl)ethyl]acetamide

HRID 2354432Notes

Reaction equation

HRID 2354432 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([CH:14]([N:22]([CH3:39])[C:23](=[O:38])[CH2:24][N:25]3[C:30]4[CH:31]=[C:32]([Cl:36])[C:33]([Cl:35])=[CH:34][C:29]=4[O:28][CH2:27][C:26]3=[O:37])[CH2:15][N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH:40]([N:43]=[C:44]=[O:45])([CH3:42])[CH3:41].C(N(CC)CC)C>ClCCl>[Cl:36][C:32]1[C:33]([Cl:35])=[CH:34][C:29]2[O:28][CH2:27][C:26](=[O:37])[N:25]([CH2:24][C:23]([N:22]([CH3:39])[CH:14]([C:11]3[CH:12]=[CH:13][C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:44]([NH:43][CH:40]([CH3:42])[CH3:41])=[O:45])[CH:3]=4)=[CH:9][CH:10]=3)[CH2:15][N:16]3[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)=[O:38])[C:30]=2[CH:31]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 61277Isopropyl isocyanateHCID 57489027N-[1-(3'-amino-4-biphenylyl)-2-(4-morpholinyl)ethyl]-2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methylacetamide

Product 1

HCID 574890322-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methyl-N-[1-[3'-({[(1-methylethyl)amino]carbonyl}amino)-4-biphenylyl]-2-(4-morpholinyl)ethyl]acetamideYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-[1-(3′-amino-4-biphenylyl)-2-(4-morpholinyl)ethyl]-2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methylacetamide (52 mg, 0.6 mmol) in dichloromethane (1 mL) was added isopropylisocyanate (36.5 mg, 0.51 mmol). Triethylamine (60 mg, 0.60 mmol) was added and the resultant mixture was stirred at room temperature for 18 h. The mixture was concentrated under reduced pressure and the residue was purified by Gilson preparative HPLC (Sunfire Prep C18, 30×150 mm, 50 mL/min, A: acetonitrile with 0.1% TFA B: water with 0.1% TFA, A: 30 to 60% over 12 min, UV detection at 214 nm) to give 40.8 mg (52%) of the title compound as off white solid. MS (ES) m/e 654.3 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customthe residue was purified by Gilson preparative HPLC (Sunfire Prep C18, 30×150 mm, 50 mL/min

Sources & evidence

ORD record
ord-be02543cd1a64fe29ba102ff324b7bbd
Source dataset
uspto-grants-2010_07
Patent number
US07749998B2

Reaction notes

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