4-Chlorobenzoic Acid → 4-chloro-N-[1-[[(4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl]carbamoyl]cyclopropyl]benzamide

HRID 2068558Notes

Reaction equation

HRID 2068558 reaction equation
[NH2:1][C:2]1([C:5]([NH:7][C@@H:8]2[CH2:14][CH2:13][C:12]3[CH:15]=[CH:16][CH:17]=[CH:18][C:11]=3[N:10]3[CH:19]=[CH:20][N:21]=[C:9]23)=[O:6])[CH2:4][CH2:3]1.[Cl:22][C:23]1[CH:31]=[CH:30][C:26]([C:27](O)=[O:28])=[CH:25][CH:24]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[Cl:22][C:23]1[CH:31]=[CH:30][C:26]([C:27]([NH:1][C:2]2([C:5](=[O:6])[NH:7][C@@H:8]3[CH2:14][CH2:13][C:12]4[CH:15]=[CH:16][CH:17]=[CH:18][C:11]=4[N:10]4[CH:19]=[CH:20][N:21]=[C:9]34)[CH2:3][CH2:4]2)=[O:28])=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 63184-Chlorobenzoic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 583040891-Amino-N-[(4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl]cyclopropanecarboxamide

Product 1

HCID 532420154-chloro-N-[1-[[(4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl]carbamoyl]cyclopropyl]benzamideYield 80%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combine 1-amino-N-[(4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl]cyclopropanecarboxamide (160 mg, 0.57 mmol), 4-chlorobenzoic acid (106 mg, 0.68 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (259.0 mg, 0.68 mmol;) in N,N-dimethylformamide (4 mL). Add diisopropylethylamine (DIEA) (0.25 mL, 1.42 mmol) and stir the reaction at ambient temperature for approximately 5 hours under nitrogen. Dilute the reaction with ethyl acetate, wash with sodium bicarbonate, water (2×), and brine, dry over sodium sulfate, and concentrate the organic layer under reduced pressure. Purify the residue by flash chromatography (40% EtOAc/hexanes to 100% EtOAc) to give the title compound (190.0 mg, 80%): MS (m/z): 421 (M+1).

Workup

  1. customthe reaction at ambient temperature for approximately 5 hours under nitrogen
  2. additionDilute
  3. washwash with sodium bicarbonate, water (2×), and brine
  4. dry with materialdry over sodium sulfate
  5. concentrationconcentrate the organic layer under reduced pressure
  6. customPurify the residue by flash chromatography (40% EtOAc/hexanes to 100% EtOAc)

Sources & evidence

ORD record
ord-3ff5b0403e054402860e50029f5d56d0
Source dataset
uspto-grants-2012_10
Patent number
US08299061B2

Reaction notes

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