Cesium carbonate → HCID 58456376, compound

HRID 1040134Notes

Reaction equation

HRID 1040134 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH:8]=[CH2:9])[CH:5]=[CH:4][N:3]=1.[NH2:10][C:11]1[CH:12]=[C:13]([C:18]2[S:22][C:21]([C:23]3([OH:27])[CH2:26][CH2:25][CH2:24]3)=[N:20][CH:19]=2)[CH:14]=[C:15]([CH3:17])[CH:16]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:8]([C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:10][C:11]2[CH:12]=[C:13]([C:18]3[S:22][C:21]([C:23]4([OH:27])[CH2:26][CH2:25][CH2:24]4)=[N:20][CH:19]=3)[CH:14]=[C:15]([CH3:17])[CH:16]=2)[N:7]=1)=[CH2:9]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 450801732-Chloro-4-ethenylpyrimidineHCID 584563951-[5-(3-Amino-5-methylphenyl)-2-thiazolyl]cyclobutanol

Product 1

HCID 58456376HCID 58456376, compoundYield 31.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-chloro-4-ethenylpyrimidine (400 mg, 2.85 mmol), Intermediate 15 (815 mg, 3.13 mmol), Pd(OAc)2 (70.3 mg, 0.313 mmol), Xantphos (247 mg, 0.427 mmol) and cesium carbonate (1.85 g, 5.69 mmol) in 1,4-dioxane (14 mL) was purged with nitrogen for 8 min, and heated to 100° C. overnight. The mixture was cooled to room temperature, diluted with water, and extracted with EtOAc (×3). The combined organics were washed with brine, dried (sodium sulfate), concentrated, and purified by flash chromatography to afford 1-(5-{3-[(4-ethenylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)cyclobutanol (330 mg, 0.905 mmol). MS ESI: [M+H]+ m/z 365.1. 1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 8.49 (d, J=4.9, 1H), 8.01 (s, 1H), 7.97 (s, 1H), 7.53 (s, 1H), 7.07 (s, 1H), 6.94 (d, J=5.1, 1H), 6.71 (dd, J=10.5, 17.4, 1H), 6.51 (s, 1H), 6.49 (d, J=16.1, 1H), 5.70 (d, J=10.5, 1H), 2.56-1.85 (m, 6H), 2.31 (s, 3H). rhSYK activity=+++

Workup

  1. customwas purged with nitrogen for 8 min
  2. temperatureThe mixture was cooled to room temperature
  3. additiondiluted with water
  4. extractionextracted with EtOAc (×3)
  5. washThe combined organics were washed with brine
  6. dry with materialdried (sodium sulfate)
  7. concentrationconcentrated
  8. custompurified by flash chromatography

Sources & evidence

ORD record
ord-2b779d52d2af4f5d8e7b6504c0c804e2
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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