Isobutyl chloroformate → HCID 59375156, compound

HRID 661925Notes

Reaction equation

HRID 661925 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]([C:20]2[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=2[F:27])=[C:8]2[C:16]=1[NH:15][C:14]1[CH2:13][CH:12]([C:17](O)=[O:18])[CH2:11][CH2:10][C:9]2=1)(=[O:3])[NH2:2].ClC(OCC(C)C)=O.Cl.[CH3:37][NH:38][O:39][CH3:40]>C1COCC1.O.C(Cl)Cl>[F:26][C:25]1[CH:24]=[CH:23][CH:22]=[C:21]([F:27])[C:20]=1[C:7]1[CH:6]=[CH:5][C:4]([C:1]([NH2:2])=[O:3])=[C:16]2[C:8]=1[C:9]1[CH2:10][CH2:11][CH:12]([C:17]([N:38]([O:39][CH3:40])[CH3:37])=[O:18])[CH2:13][C:14]=1[NH:15]2

Participants

7

Reactant 3

HCID 62365Isobutyl chloroformateHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 66606608HCID 66606608, compound2×

Product 1

HCID 59375156HCID 59375156, compoundYield 99.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 8-carbamoyl-5-(2,6-difluorophenyl)-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylic acid (Intermediate 23-3, 720 mg, 1.944 mmol) and TEA (1.084 mL, 7.78 mmol) in THF (5 mL) was treated with isobutyl chloroformate (266 mg, 1.944 mmol) at 0° C. After stirring for 10 min, a solution of N,O-dimethylhydroxylamine hydrochloric acid salt (190 mg, 1.944 mmol) in THF (2 mL) and water (0.5 mL) was added. The mixture was stirred for 30 min, then diluted with DCM, washed with NaHCO3 (aq) and water, and dried and concentrated. The residue was purified by column chromatography (eluting with EtOAc) to provide 5-(2,6-difluorophenyl)-N2-methoxy-N2-methyl-2,3,4,9-tetrahydro-1H-carbazole-2,8-dicarboxamide as a white solid (802 mg, 93%). 1H NMR (400 MHz, chloroform-d) ε1.70-1.82 (m, 1H) 1.90-1.99 (m, 1H) 2.19-2.25 (m, 2H) 2.32-2.42 (m, 1H) 2.84-2.92 (m, 1H) 3.05-3.19 (m, 1H) 3.23 (s, 3H) 3.70 (s, 3H) 6.98-7.06 (m, 3H) 7.35-7.42 (m, 2H) 10.10 (s, 1H). Mass spectrum m/z 414.2 (M+H)+.

Workup

  1. stirringThe mixture was stirred for 30 min
  2. washwashed with NaHCO3 (aq) and water
  3. customdried
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography (eluting with EtOAc)

Sources & evidence

ORD record
ord-0409b2c200544e2ba218805314105640
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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