Sodium Carbonate → Methyl 3-(7-(3-(trifluoromethyl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate

HRID 1410104Notes

Reaction equation

HRID 1410104 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[C:5]2[N:10]=[CH:9][S:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:30]2[CH:31]=[C:32]([CH:37]=[CH:38][CH:39]=2)[C:33]([O:35][CH3:36])=[O:34])O1.C([O-])([O-])=O.[Na+].[Na+]>O.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>[F:19][C:18]([F:21])([F:20])[C:14]1[CH:13]=[C:12]([NH:11][C:4]2[C:5]3[N:10]=[CH:9][S:8][C:6]=3[N:7]=[C:2]([C:30]3[CH:31]=[C:32]([CH:37]=[CH:38][CH:39]=3)[C:33]([O:35][CH3:36])=[O:34])[N:3]=2)[CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27346513-Methoxycarbonylphenylboronic acid pinacol esterHCID 866717905-chloro-N-(3-(trifluoromethyl)phenyl)thiazolo[5,4-d]pyrimidin-7-amine

Product 1

HCID 66550340Methyl 3-(7-(3-(trifluoromethyl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoateYield 84.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

To a stirred solution of 5-chloro-N-(3-(trifluoromethyl)phenyl)thiazolo[5,4-d]pyrimidin-7-amine (330 mg, 1 mmol), methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (314 mg, 1.2 mmol) and Na2CO3 (498 mg, 4.7 mmol) in 2 mL of water and 20 mL of dioxane was added Pd(PPh3)4 (93 mg, 0.075 mmol) in one portion at room temperature under nitrogen. Then the mixture was stirred at 95° C. for 16 hours under nitrogen. The solvent was evaporated at 40° C. at reduced pressure and the residue was purified by silica gel chromatography (silica gel 200-300 mesh, eluting with a mixture of petroleum ether and ethyl acetate (4:1)) to give methyl 3-(7-(3-(trifluoromethyl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoate (365 mg, 84.8%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 9.18 (s, 1H), 8.93 (s, 1H), 8.74 (d, 1H, J=7.8 Hz), 8.61 (s, 1H), 8.21 (brs, 2H), 7.94 (d, 1H, J=7.8 Hz), 7.65-7.60 (m, 2H), 7.48-7.46 (m, 1H), 4.01 (s, 3H). LC-MS: 431 [M+H]+, 429 [M−H]−, tR=1.92 min. HPLC: 95.92% at 214 nm, 97.01% at 254 nm, tR=5.14 min.

Workup

  1. customThe solvent was evaporated at 40° C. at reduced pressure
  2. customthe residue was purified by silica gel chromatography (silica gel 200-300 mesh
  3. washeluting with a mixture of petroleum ether and ethyl acetate (4:1))

Sources & evidence

ORD record
ord-38730c33d4f54127acd4e892d2daa82d
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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