tert-butyl 4-amino-1H-pyrazole-1-carboxylate → 2-(2-(2-(2-(1H-Pyrazol-4-ylamino)-5-chloropyrimidin-4-yl)ethyl)phenyl)propanamide

HRID 592416Notes

Reaction equation

HRID 592416 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH:16]([CH3:20])[C:17]([NH2:19])=[O:18])[C:5]([Cl:21])=[CH:4][N:3]=1.[NH2:22][C:23]1[CH:24]=[N:25][N:26](C(OC(C)(C)C)=O)[CH:27]=1>CO.O>[NH:25]1[CH:24]=[C:23]([NH:22][C:2]2[N:7]=[C:6]([CH2:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[CH:16]([CH3:20])[C:17]([NH2:19])=[O:18])[C:5]([Cl:21])=[CH:4][N:3]=2)[CH:27]=[N:26]1

Participants

4

Reactant 2

HCID 59587648tert-butyl 4-amino-1H-pyrazole-1-carboxylateHCID 867123072-(2-(2-(2,5-Dichloropyrimidin-4-yl)ethyl)phenyl)propanamide

Product 1

HCID 732972062-(2-(2-(2-(1H-Pyrazol-4-ylamino)-5-chloropyrimidin-4-yl)ethyl)phenyl)propanamideYield 52%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

A solution of 2-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)propanamide A30 (0.10 g, 0.31 mmol) and tert-butyl 4-amino-1H-pyrazole-1-carboxylate (0.17 g, 0.93 mmol) was heated in MeOH:water (10:1, 5 mL) at 90° C. for 18 hours. The solvents were removed in vacuo and the crude residue was purified by silica gel column chromatography (Combiflash Rf, 0-15% MeOH in DCM). The purified fractions were combined, the solvent was removed in vacuo and the solid was sonicated in cyclohexane and filtered. The residue was dried in vacuo to give the title compound 35 as a light yellow solid (0.060 g, 52%). 1H NMR (300 MHz, d6-DMSO) δ 1.34 (d, J=7.04 Hz, 3H), 2.92-3.11 (m, 4H), 3.86 (q, J=7.04 Hz, 1H), 6.85 (brs, 1H), 7.13-7.25 (m, 4H), 7.36-7.44 (m, 1H), 7.57-87 (m, 2H), 8.37 (s, 1H), 9.63 (s, 1H). LCMS-C: rt 4.72 min; m/z 371 [M+H]+.

Workup

  1. customThe solvents were removed in vacuo
  2. customthe crude residue was purified by silica gel column chromatography (Combiflash Rf, 0-15% MeOH in DCM)
  3. customthe solvent was removed in vacuo
  4. customthe solid was sonicated in cyclohexane
  5. filtrationfiltered
  6. customThe residue was dried in vacuo

Sources & evidence

ORD record
ord-00e62413af124f9f8eafe4d7ebecbd43
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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