Diisopropylethylamine → (R)-2-(3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2,6-difluoro-4-nitrophenylamino)-2-(4-fluorophenyl)ethanol

HRID 1092255Notes

Reaction equation

HRID 1092255 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][C:13]([F:19])=[C:12](F)[C:11]=3[F:21])[CH:5]=2)[CH2:3][CH2:2]1.[NH2:22][C@H:23]([C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1)[CH2:24][OH:25].CCN(C(C)C)C(C)C>CCCCO>[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:11]([F:21])=[C:12]([NH:22][C@H:23]([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)[CH2:24][OH:25])[C:13]([F:19])=[CH:14][C:15]=3[N+:16]([O-:18])=[O:17])[CH:5]=2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 10583003(R)-2-Amino-2-(4-fluorophenyl)ethanolHCID 860798025-cyclopropyl-N-(2,3,4-trifluoro-6-nitrophenyl)-1H-pyrazol-3-amine

Product 1

HCID 86621772(R)-2-(3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2,6-difluoro-4-nitrophenylamino)-2-(4-fluorophenyl)ethanolYield 57.1%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A mixture of 5-cyclopropyl-N-(2,3,4-trifluoro-6-nitrophenyl)-1H-pyrazol-3-amine (Method 103, 0.300 g, 1.01 mmol), (R)-2-amino-2-(4-fluorophenyl)ethanol (0.172 g, 1.11 mmol) and DIEA (0.263 ml, 1.51 mmol) in n-BuOH (2 ml) was heated in a sealed tube placed in an oil bath set at 135° C. for 8 hours. The solvent was removed under reduced pressure and the residue was purified by chromatography (hexane-EtOAc=1:1) to give the title compound as an orange solid (0.25 g, 57%). 1H NMR (400 MHz) 11.88 (s, 1H), 8.57 (s, 1H), 7.70 (d, J=13.2 Hz, 1H), 7.34 (m, 2H), 7.15 (t, J=8.8 Hz, 2H), 6.61 (b, 1H), 5.38 (s, 1H), 5.07 (t, J=5.6 Hz, 1H), 4.88 (m, 1H), 3.62-3.71 (m, 2H), 1.80 (m, 1H), 0.90 (m, 2H), 0.61 (m, 2H). MS: Calcd.: 433; Found: [M+H]+ 434.

Workup

  1. temperaturewas heated in a sealed tube
  2. customplaced in an oil bath
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by chromatography (hexane-EtOAc=1:1)

Sources & evidence

ORD record
ord-4e6539904bd4475da1ae698adb9aa314
Source dataset
uspto-grants-2012_03
Patent number
US08129403B2

Reaction notes

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