Sodium borohydride → N-((4-chloro-2,6-dimethoxypyrimidin-5-yl)methyl)-3-cyclopropyl-1-ethyl-1H-pyrazol-5-amine

HRID 80858Notes

Reaction equation

HRID 80858 reaction equation
[Cl:1][C:2]1[C:7]([CH:8]=O)=[C:6]([O:10][CH3:11])[N:5]=[C:4]([O:12][CH3:13])[N:3]=1.[CH:14]1([C:17]2[CH:21]=[C:20]([NH2:22])[N:19]([CH2:23][CH3:24])[N:18]=2)[CH2:16][CH2:15]1.[BH4-].[Na+]>C1COCC1>[Cl:1][C:2]1[C:7]([CH2:8][NH:22][C:20]2[N:19]([CH2:23][CH3:24])[N:18]=[C:17]([CH:14]3[CH2:16][CH2:15]3)[CH:21]=2)=[C:6]([O:10][CH3:11])[N:5]=[C:4]([O:12][CH3:13])[N:3]=1

Participants

5

Reactant 3

HCID 4311764Sodium borohydrideHCID 109765504-Chloro-2,6-dimethoxypyrimidine-5-carbaldehydeHCID 252481973-cyclopropyl-1-ethyl-1H-pyrazol-5-amine

Product 1

HCID 86690292N-((4-chloro-2,6-dimethoxypyrimidin-5-yl)methyl)-3-cyclopropyl-1-ethyl-1H-pyrazol-5-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-chloro-2,6-dimethoxypyrimidine-5-carbaldehyde (2.4 g, 11.8 mmol), and 3-cyclopropyl-1-ethyl-1H-pyrazol-5-amine (2.15 g, 14.2 mmol) in THF was heated at 50° C. for 3 h. The flask was then removed from the heating bath and cooled in an ice bath and EtOH (13 mL) was added followed by NaBH4 (0.896 g, 23.7 mmol). The resulting mixture was left to gradually warm to rt and stir for 18 h. The excess NaBH4 was quenched slowly with saturated aqueous NH4Cl and diluted with EtOAc. The aqueous layer was further extracted with EtOAc (2×250 mL) and the combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was then purified via FCC (20-75% EtOAc/heptane) to give the title compound N-((4-chloro-2,6-dimethoxypyrimidin-5-yl)methyl)-3-cyclopropyl-1-ethyl-1H-pyrazol-5-amine. MS (ESI+) m/z 338.0 (M+H)+.

Workup

  1. customThe flask was then removed from the heating bath
  2. temperaturecooled in an ice bath
  3. additionEtOH (13 mL) was added
  4. waitThe resulting mixture was left
  5. customThe excess NaBH4 was quenched slowly with saturated aqueous NH4Cl
  6. additiondiluted with EtOAc
  7. extractionThe aqueous layer was further extracted with EtOAc (2×250 mL)
  8. dry with materialthe combined organic layers were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was then purified via FCC (20-75% EtOAc/heptane)

Sources & evidence

ORD record
ord-be0e5888cad44f5a9674e34fb05aee64
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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