Hydrochloric Acid → Syk-IN-3

HRID 1040195Notes

Reaction equation

HRID 1040195 reaction equation
C[O:2][C:3]([C@H:5]1[CH2:10][CH2:9][C@:8]([OH:31])([C:11]2[S:12][C:13]([C:16]3[CH:21]=[C:20]([NH:22][C:23]4[N:28]=[C:27]([CH3:29])[CH:26]=[CH:25][N:24]=4)[CH:19]=[C:18]([CH3:30])[CH:17]=3)=[CH:14][N:15]=2)[CH2:7][C:6]1([CH3:33])[CH3:32])=[O:4].[OH-].[Na+].Cl>CO>[OH:31][C@:8]1([C:11]2[S:12][C:13]([C:16]3[CH:21]=[C:20]([NH:22][C:23]4[N:28]=[C:27]([CH3:29])[CH:26]=[CH:25][N:24]=4)[CH:19]=[C:18]([CH3:30])[CH:17]=3)=[CH:14][N:15]=2)[CH2:9][CH2:10][C@H:5]([C:3]([OH:4])=[O:2])[C:6]([CH3:33])([CH3:32])[CH2:7]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 67250092(1S,4R)-4-hydroxy-2,2-dimethyl-4-{5-[3-methyl-5-(4-methyl-pyrimidin-2-ylamino)-phenyl]-1,3-thiazol-2-yl}-cyclohexanecarboxylic acid methyl ester

Product 1

HCID 53251189Syk-IN-3Yield 96%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of the product of Step 1 (16.5 g, 35.3 mmol) in methanol (115 mL) was added sodium hydroxide (1M, 123 mL, 123 mmol) and the mixture was heated to 70° C. for 2.5 hours. The reaction was cooled to 30° C. and hydrochloric acid (1 N, 123 mL, 123 mmol) was added. The reaction was aged for 1.5 hours and filtered to provide 15.3 g (33.7 mmol, 96%) of the title compound as a white solid. MS ESI: [M+H]+ m/z 453.0. 1H NMR (600 MHz, DMSO-d6) δ 11.98 (s, 1H), 9.55 (s, 1H), 8.32 (d, J=5.0, 1H), 7.94 (s, 1H), 7.88 (s, 1H), 7.49 (s, 1H), 7.02 (s, 1H), 6.72 (d, J=5.0, 1H), 5.86 (s, 1H), 2.34 (s, 3H), 2.27 (s, 3H), 2.14 (dd, J=12.7, 3.1, 1H), 2.00 (ddd, J=18.6, 13.2, 6.0, 1H), 1.88-1.77 (m, 3H), 1.62 (d, J=14.1, 1H), 1.55 (dq, J=13.5, 3.3, 1H), 1.09 (s, 3H), 0.97 (s, 3H). rhSYK activity=+++

Workup

  1. temperatureThe reaction was cooled to 30° C.
  2. filtrationfiltered

Sources & evidence

ORD record
ord-004e01b702614510b02b7e4fe8f2746e
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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