Cesium carbonate → 1-[5-(3-Nitro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol

HRID 410520Notes

Reaction equation

HRID 410520 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=1.[NH2:12][C:13]1[CH:14]=[C:15]([C:22]2[S:26][C:25]([C:27]3([OH:31])[CH2:30][CH2:29][CH2:28]3)=[N:24][CH:23]=2)[CH:16]=[C:17]([N+:19]([O-:21])=[O:20])[CH:18]=1.C(=O)([O-])[O-].[Cs+].[Cs+].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>O1CCOCC1.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[N+:19]([C:17]1[CH:16]=[C:15]([C:22]2[S:26][C:25]([C:27]3([OH:31])[CH2:30][CH2:29][CH2:28]3)=[N:24][CH:23]=2)[CH:14]=[C:13]([NH:12][C:2]2[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=2)[CH:18]=1)([O-:21])=[O:20]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 584562421-[5-(3-Amino-5-nitrophenyl)-1,3-thiazol-2-yl]cyclobutanol

Product 1

HCID 584561051-[5-(3-Nitro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanolYield 60.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-chloro-4-(trifluoromethyl)pyrimidine (2.04 mL, 16.9 mmol), Intermediate 22 (4.69 g, 16.1 mmol), cesium carbonate (10.5 g, 32.2 mmol), XantPhos (1.40 g, 2.41 mmol) and Pd(OAc)2 (0.361 g, 1.61 mmol) in dioxane (100 mL) was heated to 100° C. overnight. Upon completion the reaction was cooled to room temperature and was diluted with ethyl acetate (100 mL) and filtered through Celite. After in vacuo concentration, purification by chromatography on silica gel (70:30 to 20:80 hexanes:ethyl acetate) provided 4.23 g (9.67 mmol, 60%) of 1-[5-(3-nitro-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutanol as a bright yellow solid. MS APCI: [M+H]+ m/z 438.0. 1H NMR (400 MHz, Acetone): δ 9.74 (s, 1H); 8.96 (s, 1H); 8.85 (s, 1H); 8.60 (s, 1H); 8.24 (s, 1H); 8.15 (s, 1H); 7.40 (s, 1H); 5.64 (s, 1H); 2.86 (s, 2H); 2.72 (s, 2H); 2.47 (d, J=11.2 Hz, 2H). rhSYK=++.

Workup

  1. temperatureUpon completion the reaction was cooled to room temperature
  2. filtrationfiltered through Celite
  3. concentrationAfter in vacuo concentration, purification by chromatography on silica gel (70:30 to 20:80 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-13c3ffb3366f4487ad65e1376fea5b1e
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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