4-Bromobenzoyl chloride → tert-butyl (3R)-3-[(4-bromobenzoyl)(1-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl)amino]piperidine-1-carboxylate

HRID 588367Notes

Reaction equation

HRID 588367 reaction equation
[CH3:1][N:2]1[C:6]2=[C:7]([NH:11][C@@H:12]3[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]3)[N:8]=[CH:9][CH:10]=[C:5]2[CH:4]=[CH:3]1.[Br:25][C:26]1[CH:34]=[CH:33][C:29]([C:30](Cl)=[O:31])=[CH:28][CH:27]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Br:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([N:11]([C:7]2[N:8]=[CH:9][CH:10]=[C:5]3[CH:4]=[CH:3][N:2]([CH3:1])[C:6]=23)[C@@H:12]2[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]2)=[O:31])=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 685154-Bromobenzoyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 117652959(R)-tert-butyl 3-((1-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl)amino)piperidine-1-carboxylate

Product 1

HCID 117653023tert-butyl (3R)-3-[(4-bromobenzoyl)(1-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl)amino]piperidine-1-carboxylateYield 72%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Preparation 4 (R)-tert-butyl 3-((1-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl)amino)piperidine-1-carboxylate (45.0 g, 136 mmol) and 4-bromobenzoyl chloride (31.3 g, 143 mmol) in dry THF (250 mL) was added 1 M lithium bis(trimethylsilyl)amide (163 mL, 163 mmol) dropwise at 0° C. The reaction mixture was warmed to room temperature and stirred for 15 h. The reaction was quenched with aqueous NH4Cl and extracted with EtOAc (3×500 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated in vacuo. The residue was purified by recrystallization (petroleum ether:EtOAc=2:1) to afford the title compound as an off-white solid (50 g, 72%).

Workup

  1. customThe reaction was quenched with aqueous NH4Cl
  2. extractionextracted with EtOAc (3×500 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe residue was purified by recrystallization (petroleum ether:EtOAc=2:1)

Sources & evidence

ORD record
ord-6bf1c88ab7a740b6a8b1d00d52e363c2
Source dataset
uspto-grants-2016_01
Patent number
US09227956B2

Reaction notes

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