Hydrochloric Acid → HCID 178428312, compound

HRID 1482890Notes

Reaction equation

HRID 1482890 reaction equation
[F:1][CH:2]([F:34])[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]([CH2:23][C@H:24]4[CH2:29][CH2:28][C@H:27]([C:30]([O:32]C)=[O:31])[CH2:26][CH2:25]4)=[N:21][CH:22]=3)[CH:13]=[C:14]([CH3:16])[CH:15]=2)[N:4]=1.O.[OH-].[Li+].Cl>C1COCC1.O>[F:34][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]([CH2:23][C@H:24]4[CH2:29][CH2:28][C@H:27]([C:30]([OH:32])=[O:31])[CH2:26][CH2:25]4)=[N:19][CH:18]=3)[CH:13]=[C:14]([CH3:16])[CH:15]=2)[N:4]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 178501077HCID 178501077, compound

Product 1

HCID 178428312HCID 178428312, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of methyl trans-4-{[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]methyl}cyclohexanecarboxylate (60 mg, 0.13 mmol) in THF (2 mL) and water (0.5 mL) was added lithium hydroxide monohydrate (16 mg, 0.39 mmol) and then the reaction mixture was stirred at 60° C. for 8 hours. After cooling to room temperature, water was added to the mixture and the pH was adjusted to pH 2 by the addition of aqueous 1M HCl. The mixture was extracted with ethyl acetate, and the combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by prep-TLC (ethyl acetate/petroleum ether) to give trans-4-{[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]methyl}cyclohexanecarboxylic acid. MS ESI calc'd for C24H26F2N5O2 [M+H]+ 454. found 454. 1H NMR: (400 MHz, DMSO-d6) δ 10.06 (s, 1H), 8.95 (s, 2H), 8.72 (s, 1H), 8.00 (s, 1H), 7.59 (s, 1H), 7.50 (s, 1H), 7.22 (s, 1H), 7.08 (s, 1H), 6.88 (t, J=54.4 Hz, 1H), 3.14-3.13 (m, 1H), 2.79-2.77 (m, 2H), 2.35 (s, 3H), 2.07-2.04 (m, 1H), 1.87-1.84 (m, 2H), 1.66 (s, 1H), 1.30-1.21 (m, 3H), 1.07-1.03 (m, 2H).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionThe mixture was extracted with ethyl acetate
  3. dry with materialthe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by prep-TLC (ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-284c15fedbe342c78b5fc6879c526b4b
Source dataset
uspto-grants-2016_08
Patent number
US09416111B2

Reaction notes

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