Ammonium Chloride → HCID 11999001, compound

HRID 2102746Notes

Reaction equation

HRID 2102746 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:20]3[CH2:25][CH2:24][CH2:23][N:22]([C:26]([NH:28][C:29]4[CH:37]=[CH:36][C:32]([C:33](O)=[O:34])=[CH:31][CH:30]=4)=[O:27])[CH2:21]3)([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.C([N:41](C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[Cl-].[NH4+]>CN(C=O)C>[C:33]([C:32]1[CH:31]=[CH:30][C:29]([NH:28][C:26]([N:22]2[CH2:23][CH2:24][CH2:25][CH:20]([C:6]3([CH2:12][C:13]4[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=4)[C:5]4[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=4)[NH:8][C:7]3=[O:11])[CH2:21]2)=[O:27])=[CH:37][CH:36]=1)(=[O:34])[NH2:41]

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11998891HCID 11998891, compound

Product 1

HCID 11999001HCID 11999001, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of rac-4-({3-[6-chloro-3-(3-chloro-benzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-piperidine-1-carbonyl}-amino)-benzoic acid (50 mg, 0.093 mmol) (from Example 64 supra) in DMF (1.5 mL) was added diisopropyl ethylamine (48.0 mg, 0.37 mmol) (Aldrich), followed by the addition N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (35.5 mg, 0.18 mmol) (Aldrich), 1-hydroxybenzotriazole (25.0 mg, 0.18 mmol) (Aldrich) and ammonium chloride (9.8 mg, 0.18 mmol) (Aldrich). The mixture was stirred at room temperature for 2 hours and then heated at 60° C. for 2 hours. The mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried over MgSO4 and concentrated. The residue was purified by chromatography to give rac-3-[6-chloro-3-(3-chloro-benzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-piperidine-1-carboxylic acid (4-carbamoyl-phenyl)-amide as a white solid. (Yield 25 mg, 50%).

Workup

  1. temperatureheated at 60° C. for 2 hours
  2. customThe mixture was partitioned between ethyl acetate and water
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-8478c6fb36ef4010ba303b9d38a881fd
Source dataset
uspto-grants-2009_08
Patent number
US07576082B2

Reaction notes

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