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

HRID 2068534Notes

Reaction equation

HRID 2068534 reaction equation
Cl.CN(C)CCCN=C=NCC.[CH:13]1[N:17]2[C:18]3[CH:27]=[CH:26][CH:25]=[CH:24][C:19]=3[CH2:20][CH2:21][C@@H:22]([NH2:23])[C:16]2=[N:15][CH:14]=1.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[Cl:45][C:46]1[CH:60]=[CH:59][C:49]([C:50]([NH:52][C:53]2([C:56](O)=[O:57])[CH2:55][CH2:54]2)=[O:51])=[CH:48][CH:47]=1>C1COCC1>[Cl:45][C:46]1[CH:60]=[CH:59][C:49]([C:50]([NH:52][C:53]2([C:56](=[O:57])[NH:23][C@@H:22]3[CH2:21][CH2:20][C:19]4[CH:24]=[CH:25][CH:26]=[CH:27][C:18]=4[N:17]4[CH:13]=[CH:14][N:15]=[C:16]34)[CH2:54][CH2:55]2)=[O:51])=[CH:48][CH:47]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 583040411-[(4-Chlorobenzoyl)amino]cyclopropanecarboxylic acidHCID 58304055(R)-5,6-Dihydro-4H-benzo[F]imidazo[1,2-A]azepin-4-amine

Product 1

HCID 532420154-chloro-N-[1-[[(4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-yl]carbamoyl]cyclopropyl]benzamideYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (29 g, 151 mmol) to a 10° C. slurry of (4R)-5,6-dihydro-4H-imidazo[1,2-a][1]benzazepin-4-amine (30 g, 151 mmol), 1-hydroxybenzotriazole (20 g, 151 mmol), triethylamine (41.97 mL, 301 mmol), and 1-[(4-chlorobenzoyl)amino]cyclopropanecarboxylic acid (40 g, 166 mmol) in THF (300 mL). Remove the ice bath, warm the mixture to ambient temperature, and stir it for 4 hours. Pour the mixture into water (1.0 L) and extract with ethyl acetate (1.0 L). Wash the organic phase with saturated sodium bicarbonate (500 mL), dry over magnesium sulfate, filter, and concentrate under reduced pressure. Slurry the residue in ethyl acetate (300 mL) and heat to 71° C. Cool to ambient temperature, filter the precipitate, and wash with ethyl acetate (100 mL) to give the title compound (38.8 g, 61%): MS (m/z): 421 (M+1).

Workup

  1. customRemove the ice bath
  2. additionPour the mixture into water (1.0 L)
  3. extractionextract with ethyl acetate (1.0 L)
  4. washWash the organic phase with saturated sodium bicarbonate (500 mL)
  5. dry with materialdry over magnesium sulfate
  6. filtrationfilter
  7. concentrationconcentrate under reduced pressure
  8. temperatureheat to 71° C
  9. temperatureCool to ambient temperature
  10. filtrationfilter the precipitate
  11. washwash with ethyl acetate (100 mL)

Sources & evidence

ORD record
ord-10cd7c9ea84f46718aae6c789809fe6c
Source dataset
uspto-grants-2012_10
Patent number
US08299061B2

Reaction notes

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