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Acetic Acid → 1-(5-{3-[(4-Cyclobutylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)cyclobutanol

HRID 1040138
Notes
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Reaction equation

HRID 1040138 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH:8]2[CH2:11][CH2:10][CH2:9]2)[CH:5]=[CH:4][N:3]=1.[NH2:12][C:13]1[CH:14]=[C:15]([C:20]2[S:24][C:23]([C:25]3([OH:29])[CH2:28][CH2:27][CH2:26]3)=[N:22][CH:21]=2)[CH:16]=[C:17]([CH3:19])[CH:18]=1.C(O)(=O)C>O1CCOCC1>[CH:8]1([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:12][C:13]3[CH:14]=[C:15]([C:20]4[S:24][C:23]([C:25]5([OH:29])[CH2:28][CH2:27][CH2:26]5)=[N:22][CH:21]=4)[CH:16]=[C:17]([CH3:19])[CH:18]=3)[N:7]=2)[CH2:11][CH2:10][CH2:9]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 497584742-Chloro-4-cyclobutylpyrimidineHCID 584563951-[5-(3-Amino-5-methylphenyl)-1,3-thiazol-2-yl]cyclobutanol

Product 1

HCID 584560801-(5-{3-[(4-Cyclobutylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)cyclobutanolYield 44%

Reagents, catalysts & solvents 1

HCID 31275
1,4-Dioxane
Solvent

Conditions

Temperature
120 °C

Procedure

2-Chloro-4-cyclobutylpyrimidine (65 mg, 0.39 mmol), Intermediate 15 (100 mg, 0.39 mmol), and acetic acid (22 μL, 0.39 mmol) were combined in dioxane (1.9 mL) and the mixture was stirred at 120° C. for 3 h. The mixture was cooled to room temperature and directly purified by Combiflash chromatography on silica gel, eluting with ethyl acetate/isohexane to provide 66 mg (0.17 mmol, 44%) of 1-(5-{3-[(4-cyclobutylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)cyclobutanol. MS ESI: [M+H]+ m/z 393.2. 1H NMR (600 MHz, DMSO-d6) δ 9.56 (s, 1H), 8.33 (d, J=4.8, 1H), 8.12 (s, 1H), 7.95 (s, 1H), 7.48 (s, 1H), 7.05 (s, 1H), 6.68 (d, J=5.4, 1H), 6.46 (s, 1H), 3.53-3.50 (m, 1H), 2.52-2.46 (m, 2H), 2.33-2.22 (m, 9H), 1.99 (m, 1H), 1.87-1.83 (m, 3H). rhSYK activity=+++

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customdirectly purified by Combiflash chromatography on silica gel
  3. washeluting with ethyl acetate/isohexane

Sources & evidence

ORD record
ord-32246bf22e384639afb319b6b5bc26dd
Source dataset
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08551984B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes