Diisopropylethylamine → 2,2-Diallyl-3-isobutyl-N4-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-succinamide

HRID 1635109

Reaction equation

HRID 1635109 reaction equation
[CH2:1]([C:4]([CH:11]([C:16](=[O:37])[NH:17][CH:18]1[C:24](=[O:25])[N:23]([CH3:26])[C:22]2[CH:27]=[CH:28][CH:29]=[CH:30][C:21]=2[C:20]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[N:19]1)[CH2:12][CH:13]([CH3:15])[CH3:14])([CH2:8][CH:9]=[CH2:10])[C:5](O)=[O:6])[CH:2]=[CH2:3].C[N:39](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C.O>[CH2:1]([C:4]([CH2:8][CH:9]=[CH2:10])([CH:11]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:16]([NH:17][CH:18]1[C:24](=[O:25])[N:23]([CH3:26])[C:22]2[CH:27]=[CH:28][CH:29]=[CH:30][C:21]=2[C:20]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)=[N:19]1)=[O:37])[C:5]([NH2:39])=[O:6])[CH:2]=[CH2:3]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 222882322-Allyl-2-[3-methyl-1-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e] [1,4]diazepin-3-ylcarbamoyl)-butyl]-pent-4-enoic acid

Product 1

HCID 221352682,2-Diallyl-3-isobutyl-N4-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-succinamideYield 48%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 30 (250 mg, 0.5 mmol) in 30 ml DMF was added HATU (250 mg, 0.66 mmol) and DIEA (400 uL, 2.2 mmol). After stirring for 2 hrs, ammonia gas was bubbled into the solution for 5 minutes using a glass inlet tube. The mixture was then stirred at ambient temperature overnight. Water was added (10 mL) and the solvent was removed under vacuum to give a yellow oil which was taken up in ethyl acetate and water (1:1). The organic layer was washed twice with water and then brine, and dried over Na2SO4. After filtration and concentration, the crude product was purified using silica gel chromatography (CH2Cl2/methanol 10:0.5) to give compound 31 (120 mg) as a white solid (48%). 1H NMR (CDCl3) 0.95-0.88 (dd, 6H), 1.32-1.28 (m, 1H), 1.64-1.50 (m, 1H), 1.90-1.80 (m, 1H), 2.35-2.00 (m, 1H), 2.80-2.54 (m, 4H), 3.48 (s, 3H), 5.38-5.14 (m, 5H), 5.54-5.51 (d, 1H), 5.90-5.78 (m, 2H), 7.65-7.25 (m, 9H), 8.52 (s, 1H). ESI ES+=523.2 (M+Na).

Workup

  1. customammonia gas was bubbled into the solution for 5 minutes
  2. stirringThe mixture was then stirred at ambient temperature overnight
  3. additionWater was added (10 mL)
  4. customthe solvent was removed under vacuum
  5. customto give a yellow oil which
  6. washThe organic layer was washed twice with water
  7. dry with materialbrine, and dried over Na2SO4
  8. filtrationAfter filtration and concentration
  9. customthe crude product was purified

Sources & evidence

ORD record
ord-b03f45b74cc844079691a1ab180a6f1d
Source dataset
uspto-grants-2003_01
Patent number
US06509333B2

Linked notes

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