Ammonium Hydroxide → HCID 57750397, compound

HRID 422995Notes

Reaction equation

HRID 422995 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][C:11]([C:13]2([C:28]#[N:29])[CH2:18][CH2:17][N:16]([C:19]3[C:20]4[CH:27]=[CH:26][NH:25][C:21]=4[N:22]=[CH:23][N:24]=3)[CH2:15][CH2:14]2)=[O:12])[CH3:9])=[CH:4][CH:3]=1.[OH-].[NH4+]>C(O)C.[Ni]>[NH2:29][CH2:28][C:13]1([C:11]([NH:10][C@@H:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[CH3:9])=[O:12])[CH2:14][CH2:15][N:16]([C:19]2[C:20]3[CH:27]=[CH:26][NH:25][C:21]=3[N:22]=[CH:23][N:24]=2)[CH2:17][CH2:18]1

Participants

5

Reactant 2

HCID 14923Ammonium HydroxideHCID 57750288HCID 57750288, compound2×

Product 1

HCID 57750397HCID 57750397, compoundYield 58.6%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 702EthanolSolvent

Procedure

Raney® nickel (293 mg, 1.71 mmol) was added to a solution of (R)—N-(1-(4-chlorophenyl)ethyl)-4-cyano-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (Intermediate 45) (466 mg, 1.14 mmol), in ethanol (30 mL). Ammonium hydroxide (10 mL) was added. This mixture was first purged with nitrogen, then placed under a balloon of hydrogen and stirred for 36 hours. The reaction mixture was filtered through celite and the solvent evaporated to dryness. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% 7N ammonia/MeOH in DCM. Pure fractions were evaporated to dryness to afford (R)-4-(aminomethyl)-N-(1-(4-chlorophenyl)ethyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (276 mg, 58.6%) as a white solid.

Workup

  1. customThis mixture was first purged with nitrogen
  2. filtrationThe reaction mixture was filtered through celite
  3. customthe solvent evaporated to dryness
  4. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 10% 7N ammonia/MeOH in DCM
  5. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-25b44a0ed76840bdaa2735f569ab9778
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

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