Hydrochloric Acid → HCID 58456384, compound

HRID 410631Notes

Reaction equation

HRID 410631 reaction equation
C([O:8][CH:9]1[CH2:14][CH2:13][CH:12]([O:15][C:16]2[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C:23]3[CH:24]=[C:25]([C:30]4[S:34][C:33]([C:35]([OH:41])([CH3:40])[C:36]([F:39])([F:38])[F:37])=[N:32][CH:31]=4)[CH:26]=[C:27]([CH3:29])[CH:28]=3)[N:17]=2)[CH2:11][CH2:10]1)C1C=CC=CC=1.Cl>CO>[CH3:29][C:27]1[CH:28]=[C:23]([NH:22][C:18]2[N:17]=[C:16]([O:15][CH:12]3[CH2:11][CH2:10][CH:9]([OH:8])[CH2:14][CH2:13]3)[CH:21]=[CH:20][N:19]=2)[CH:24]=[C:25]([C:30]2[S:34][C:33]([C:35]([OH:41])([CH3:40])[C:36]([F:38])([F:39])[F:37])=[N:32][CH:31]=2)[CH:26]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67430445HCID 67430445, compound

Product 1

HCID 58456384HCID 58456384, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To 2-(5-{3-[(4-{[4-(benzyloxy)cyclohexyl]oxy}pyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,1,1-trifluoropropan-2-ol (Example 94B-3, 0.12 g, 0.21 mmol) was added methanol (0.70 mL) and concentrated hydrochloric acid (6.2 μL, 0.21 mmol). The solution was evacuated and then purged with argon 5 times. 10% Palladium on carbon (0.002 g) was added and the solution was evacuated and then purged with argon 3 times. A balloon filled with hydrogen was placed on top of the reaction and the reaction was evacuated and then backfilled with hydrogen 3 times. The reaction was stirred for four hours. The solution was then filtered carefully through celite. The filtrate was concentrated and purified by reverse phase HPLC (10-100% acetonitrile gradient with water over 12 minutes with a 0.05% trifluoroacetic acid buffer) to afford 4-{[2-({3-methyl-5-[2-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1,3-thiazol-5-yl]phenyl}amino)pyrimidin-4-yl]oxy}cyclohexanol (30 mg, 0.06 mmol, 30%) as a 60:40 mixture of diastereomers. MS ESI: [M+H]+ m/z 494.7. The following NMR data for the major isomer: 1H NMR (500 MHz, DMSO-d6) δ 9.52 (s, 1H), 8.22-8.15 (m, 1H), 8.08 (s, 1H), 7.74 (s, 1H), 7.68-7.60 (m, 2H), 7.11 (s, 1H), 6.31-6.13 (m, 1H), 5.08-4.93 (m, 1H), 4.65-4.53 (m, 1H), 3.54-3.42 (m, 1H), 2.33 (s, 3H), 2.09-1.98 (m, 1H), 1.91-1.72 (m, 5H), 1.59-1.37 (m, 2H), 1.32-1.19 (m, 2H), 1.12-1.03 (m, 1H). rhSYK activity=+++

Workup

  1. customThe solution was evacuated
  2. custompurged with argon 5 times
  3. addition10% Palladium on carbon (0.002 g) was added
  4. customthe solution was evacuated
  5. custompurged with argon 3 times
  6. additionA balloon filled with hydrogen
  7. customwas placed on top of the reaction
  8. customthe reaction was evacuated
  9. filtrationThe solution was then filtered carefully through celite
  10. concentrationThe filtrate was concentrated
  11. custompurified by reverse phase HPLC (10-100% acetonitrile gradient with water over 12 minutes with a 0.05% trifluoroacetic acid buffer)

Sources & evidence

ORD record
ord-905eb765b9b449f68bfb32a488887309
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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