ethyl rel-(1R,2S)-4-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethenyl}-2-methylcyclohexanecarboxylate → ethyl rel-(1R,2S)-4-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethyl}-2-methylcyclohexanecarboxylate

HRID 1482899Notes

Reaction equation

HRID 1482899 reaction equation
[F:1][CH:2]([F:37])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([NH:9][C:10]2[CH:11]=[C:12]([C:17]3[CH:18]=[N:19][C:20]([C:23]([CH:25]4[CH2:30][CH2:29][C@@H:28]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[C@@H:27]([CH3:36])[CH2:26]4)=[CH2:24])=[N:21][CH:22]=3)[CH:13]=[C:14]([CH3:16])[CH:15]=2)[N:4]=1>[Pd].C1COCC1>[F:37][CH:2]([F:1])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([NH:9][C:10]2[CH:11]=[C:12]([C:17]3[CH:22]=[N:21][C:20]([CH:23]([CH:25]4[CH2:30][CH2:29][C@@H:28]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[C@@H:27]([CH3:36])[CH2:26]4)[CH3:24])=[N:19][CH:18]=3)[CH:13]=[C:14]([CH3:16])[CH:15]=2)[N:4]=1

Participants

4

Reactant 1

HCID 118126870ethyl rel-(1R,2S)-4-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethenyl}-2-methylcyclohexanecarboxylate

Product 1

HCID 118126847ethyl rel-(1R,2S)-4-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethyl}-2-methylcyclohexanecarboxylate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of ethyl rel-(1R,2S)-4-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethenyl}-2-methylcyclohexanecarboxylate (592 mg, 1.17 mmol) and palladium on carbon (50 mg) in THF (10 mL) was stirred at 30° C. for 16 hours under a hydrogen atmosphere (45 psi). The mixture was then filtered and concentrated under reduced pressure. The residue was purified by prep-TLC (ethyl acetate/petroleum ether) to give ethyl rel-(1R,2S)-4-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethyl}-2-methylcyclohexanecarboxylate. MS ESI calc'd for C28H34F2N5O2[M+H]+ 510. found 510. 1H NMR: (400 MHz, CD3OD) δ 8.98 (d, J=1.0 Hz, 2H), 8.64 (d, J=4.8 Hz, 1H), 7.99 (s, 1H), 7.60 (s, 1H), 7.19 (s, 1H), 7.04 (d, J=5.0 Hz, 1H), 6.58 (t, J=54.4 Hz, 1H), 4.15-4.06 (m, 2H), 2.87-2.75 (m, 2H), 2.44 (s, 3H), 2.02 (br s, 2H), 1.90-1.58 (m, 4H), 1.37-1.30 (m, 5H), 1.24-1.19 (m, 3H), 1.00-0.86 (m, 3H).

Workup

  1. filtrationThe mixture was then filtered
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by prep-TLC (ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-87af97aef9b140f8b8558b70ea8a78df
Source dataset
uspto-grants-2016_08
Patent number
US09416111B2

Reaction notes

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