Hydrochloric Acid → HCID 178428311, compound

HRID 1482894Notes

Reaction equation

HRID 1482894 reaction equation
[F:1][CH:2]([F:35])[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]([CH:23]([C@H:25]4[CH2:30][CH2:29][C@H:28]([C:31]([O:33]C)=[O:32])[CH2:27][CH2:26]4)[CH3:24])=[N:21][CH:22]=3)[CH:13]=[C:14]([CH3:16])[CH:15]=2)[N:4]=1.[OH-].[Li+].Cl>C1COCC1.O.[Cl-].[Na+].O>[F:35][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]([C@H:25]4[CH2:30][CH2:29][C@H:28]([C:31]([OH:33])=[O:32])[CH2:27][CH2:26]4)[CH3:24])=[N:19][CH:18]=3)[CH:13]=[C:14]([CH3:16])[CH:15]=2)[N:4]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 178501081HCID 178501081, compound

Product 1

HCID 178428311HCID 178428311, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of methyl trans-4-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethyl}cyclohexanecarboxylate (isomer 1) (20 mg, 0.042 mmol) in THF (2 mL) and water (0.5 mL) was added lithium hydroxide (3.0 mg, 0.12 mmol), and the mixture was stirred for 8 hours at 60° C. After cooling to room temperature, the mixture was adjusted to pH 2 by adding 1 M aqueous hydrochloric acid, diluted with brine, and extracted with ethyl acetate (3×100 mL). 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-{1-[5-(3-{[4-(difluoromethyl)pyrimidin-2-yl]amino}-5-methylphenyl)pyrimidin-2-yl]ethyl}cyclohexanecarboxylic acid, isomer 1 (example 6.1). MS ESI calc'd for C25H28F2N5O2 [M+H]+ 468. found 468. 1H NMR: (400 MHz, DMSO-d6) δ 10.08 (s, 1H), 8.99 (s, 2H), 8.74-8.73 (m, 1H), 8.02 (s, 1H), 7.61 (s, 1H), 7.24 (s, 1H), 7.10-7.09 (m, 1H), 6.91 (t, J=54 Hz, 1H), 2.84-2.80 (m, 1H), 2.37 (s, 3H), 2.13-2.07 (m, 1H), 1.96-1.81 (m, 3H), 1.73-1.71 (m, 1H), 1.36-1.06 (m, 8H).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ethyl acetate (3×100 mL)
  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-67173dd64721448a91d9d62bcf927078
Source dataset
uspto-grants-2016_08
Patent number
US09416111B2

Reaction notes

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