Sodium Carbonate → HCID 71209398, compound

HRID 1485265Notes

Reaction equation

HRID 1485265 reaction equation
C([O-])([O-])=O.[Na+].[Na+].Cl[C:8]1[C:13]([C:14]([F:17])([F:16])[F:15])=[CH:12][N:11]=[C:10]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([CH:25]3[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]3)=[CH:21][CH:20]=2)[N:9]=1.CC1(C)C(C)(C)OB(/[CH:46]=[CH:47]/[C:48]2[CH:49]=[C:50]([CH:55]=[CH:56][N:57]=2)[C:51]([O:53][CH3:54])=[O:52])O1.[Li+].[Cl-]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:34]([O:33][C:31]([N:28]1[CH2:29][CH2:30][CH:25]([C:22]2[CH:23]=[CH:24][C:19]([NH:18][C:10]3[N:9]=[C:8](/[CH:46]=[CH:47]/[C:48]4[CH:49]=[C:50]([CH:55]=[CH:56][N:57]=4)[C:51]([O:53][CH3:54])=[O:52])[C:13]([C:14]([F:17])([F:16])[F:15])=[CH:12][N:11]=3)=[CH:20][CH:21]=2)[CH2:26][CH2:27]1)=[O:32])([CH3:37])([CH3:36])[CH3:35]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 68282875HCID 68282875, compoundHCID 86675716Tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 71209398HCID 71209398, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

An aqueous 2.0 M solution of Na2CO3 (0.3 mL) was added to a solution of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I45) (100 mg, 0.103 mmol), (E)-methyl 2-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)isonicotinate (1127) (76 mg, 0.26 mmol), Pd(PPh3)4 (75 mg, 0.66 mmol), LiCl (28 mg, 0.66 mmol) in 1,4-dioxane (5 mL) and the resulting mixture was stirred under nitrogen at 90° C. for 16 hours. The crude mixture was evaporated under reduced pressure and adsorbed onto silica gel. Chromatography (SiO2, 0-50% ethyl acetate/petroleum benzine 40-60° C.) gave the title compound (I128) (110 mg, 86%) as a yellow solid; 1H NMR (400 MHz, CDCl3) δ 8.84 (d, J=4.9 Hz, 1H), 8.64 (s, 1H), 8.14 (d, J=15.1 Hz, 1H), 8.02 (s, 1H), 7.88 (dd, J=15.1, 1.6 Hz, 1H), 7.80 (dd, J=4.9, 1.5 Hz, 1H), 7.60 (d, J=8.5 Hz, 2H), 7.36 (s, 1H), 7.25 (m, 1H), 4.33-4.19 (m, 2H), 4.00 (s, 3H), 2.82 (m, 2H), 2.67 (m, 1H), 1.85 (d, J=12.7 Hz, 2H), 1.64 (dd, J=12.5, 4.0 Hz, 2H), 1.59 (s, 9H). LCMS Method C: rt 6.93 min; m/z 584.21 [M+1]+, 582.1 [M−1]−, 528.1 [M-tBu+2]+.

Workup

  1. customThe crude mixture was evaporated under reduced pressure

Sources & evidence

ORD record
ord-487b5a80a5704c1290f0ead483134f27
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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