Cesium carbonate → 5-(3,3-Difluoro-azetidin-1-yl)-6-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (1-methyl-1-thiazol-2-yl-ethyl)-amide

HRID 927734Notes

Reaction equation

[CH3:1][C:2]([NH:9][C:10]([C:12]1[CH:17]=[CH:16][C:15](Br)=[C:14]([O:19][CH2:20][C:21]([F:24])([F:23])[F:22])[N:13]=1)=[O:11])([C:4]1[S:5][CH:6]=[CH:7][N:8]=1)[CH3:3].Cl.[F:26][C:27]1([F:31])[CH2:30][NH:29][CH2:28]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][C:2]([NH:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([N:29]2[CH2:30][C:27]([F:31])([F:26])[CH2:28]2)=[C:14]([O:19][CH2:20][C:21]([F:24])([F:23])[F:22])[N:13]=1)=[O:11])([C:4]1[S:5][CH:6]=[CH:7][N:8]=1)[CH3:3]

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of 5-bromo-6-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (1-methyl-1-thiazol-2-yl-ethyl)-amide (Example 288a) (63.6 mg, 150 μmol) in dry toluene (1 ml) was added 3,3-difluoroazetidine hydrochloride (21.4 mg, 165 μmol), BINAP (9.34 mg, 15.0 μmol), Pd(OAc)2 (3.37 mg, 15.0 μmol) and Cs2CO3 (122 mg, 375 μmol). The reaction was stirred at 120° C. overnight and controlled by LC-MS. Evaporation of the volatiles, residue was redissolved in DMF and directly purified by preparative HPLC to give the title compound (21 mg, 48 umol, 32%), MS (EI): m/e=437.4 [M+H]+.

Workup

customEvaporation of the volatiles, residue
dissolutionwas redissolved in DMF
customdirectly purified by preparative HPLC

Sources & evidence

ORD record: ord-e78752c843384667b99443171c0c1c8e
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290451B2

Reaction notes

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