Hydrochloric Acid → HCID 59375159, compound

HRID 661926Notes

Reaction equation

HRID 661926 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:21]=[CH:20][C:19]([C:22]([NH2:24])=[O:23])=[C:18]2[C:10]=1[C:11]1[CH2:12][CH2:13][CH:14]([C:25](N(OC)C)=[O:26])[CH2:15][C:16]=1[NH:17]2.[CH3:31][Mg]Br.Cl>C1COCC1>[C:25]([CH:14]1[CH2:13][CH2:12][C:11]2[C:10]3[C:18](=[C:19]([C:22]([NH2:24])=[O:23])[CH:20]=[CH:21][C:9]=3[C:3]3[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=3[F:8])[NH:17][C:16]=2[CH2:15]1)(=[O:26])[CH3:31]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 59375156HCID 59375156, compoundHCID 178418573HCID 178418573, compound2×

Product 1

HCID 59375159HCID 59375159, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-(2,6-difluorophenyl)-N2-methoxy-N2-methyl-2,3,4,9-tetrahydro-1H-carbazole-2,8-dicarboxamide (Example 26-1, 719 mg, 1.739 mmol) in THF (1 mL) was treated with methylmagnesium bromide (3 M in diethyl ether, 2.90 mL, 8.70 mmol) at 0° C. After 20 min, additional methylmagnesium bromide (2.90 mL, 8.70 mmol) was added and stirring was continued for 30 min more. The mixture was treated with 1 M hydrochloric acid and extracted four times with DCM. The combined organic phases were washed with water, dried and concentrated. The residue was purified by column chromatography (eluting with hexane-EtOAc) and the resulting material was triturated with DCM to provide 2-acetyl-5-(2,6-difluorophenyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide as an off-white solid (210 mg, 33%). 1H NMR (400 MHz, methanol-d4) δ 7.59 (1H, d, J=7.91 Hz), 7.39-7.49 (2H, m), 7.01-7.09 (3H, m), 6.90 (1H, d, J=7.91 Hz), 2.86-2.97 (3H, m), 2.24-2.33 (1H, m), 2.22 (3H, s), 2.01-2.18 (2H, m), 1.54-1.66 (1H, m). Mass spectrum m/z 369.1 (M+H)+.

Workup

  1. waitwas continued for 30 min
  2. extractionextracted four times with DCM
  3. washThe combined organic phases were washed with water
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (eluting with hexane-EtOAc)
  7. customthe resulting material was triturated with DCM

Sources & evidence

ORD record
ord-08982952a7f9495794049feb9054ec61
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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