Aniline → HCID 19063686, compound

HRID 482353Notes

Reaction equation

HRID 482353 reaction equation
[CH:1]([C:4]([C:30]1[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=1)([C:27](=[O:29])[NH2:28])[N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[C:9]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:8][CH:7]([CH2:22][C:23](O)=[O:24])[C:6]1=[O:26])([CH3:3])[CH3:2].[NH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH:1]([C:4]([C:30]1[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=1)([C:27](=[O:29])[NH2:28])[N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[C:9]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[N:8][CH:7]([CH2:22][C:23]([NH:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[O:24])[C:6]1=[O:26])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6115AnilineHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 67694150HCID 67694150, compound

Product 1

HCID 19063686HCID 19063686, compoundYield 60.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

According to Process F, a mixture of {1-[Isopropyl-(4-methoxy-phenyl)-carbamoylmethyl]-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl}-acetic acid (200 mg, 0.400 mmol), prepared as in Intermediate 29, aniline (0.033 mL, 0.356 mmol), and bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (167 mg, 0.356 mmol) in anhydrous DCM (3 mL) is treated with diisopropylethylamine (0.170 mL, 0.978 mmol) and stirred at ambient temperature under nitrogen. After 1.5 hrs., the solvent is removed in vacuo and the residue is purified by chromatography on flash grade silica gel using 60% ethyl acetate in n-hexane. Fractions containing the product are combined, concentrated in vacuo and triturated with n-hexane. After removing the solvent in vacuo, the product is dried overnight at ambient temperature under high vacuum to provide the title compound (123 mg, 0.214 mmol) as a white solid. The product is lyophilized from acetonitrile/water. 1H NMR (300 MHz, d6-DMSO) δ=0.86-0.96 (m, 6H); 3.14 (d, J=6.9 Hz, 2H); 3.77 (S, 3H); 4.03-6.12 (M, 2H); 4.23 (D, J=16.8 HZ, 1H); 4.59-6.73 (M, 1H); 6.97-7.08 (M, 3H); 7.15-7.32 (M, 6H); 7.36-7.66 (M, 9H); 10.15 (S, 1H). MS (FAB): [M+H]+ =575.

Workup

  1. custom, the solvent is removed in vacuo
  2. customthe residue is purified by chromatography on flash grade silica gel using 60% ethyl acetate in n-hexane
  3. additionFractions containing the product
  4. concentrationconcentrated in vacuo
  5. customtriturated with n-hexane
  6. customAfter removing the solvent in vacuo
  7. customthe product is dried overnight at ambient temperature under high vacuum

Sources & evidence

ORD record
ord-fa574fcc3a474245bbd6ab8d6768591f
Source dataset
uspto-grants-1998_08
Patent number
US05795887

Reaction notes

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