Cesium carbonate → 4-(2-Methylsulfanyl-5,7-dihydro-pyrrolo[3,4-d]pyrimidin-6-yl)-pyridine-2-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 1052042Notes

Reaction equation

HRID 1052042 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)=[O:9])[CH:3]=1.[CH3:21][S:22][C:23]1[N:24]=[CH:25][C:26]2[CH2:31][NH:30][CH2:29][C:27]=2[N:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[F:18][C:17]([F:20])([F:19])[C:13]1[CH:12]=[C:11]([NH:10][C:8]([C:4]2[CH:3]=[C:2]([N:30]3[CH2:31][C:26]4[CH:25]=[N:24][C:23]([S:22][CH3:21])=[N:28][C:27]=4[CH2:29]3)[CH:7]=[CH:6][N:5]=2)=[O:9])[CH:16]=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 670658482-(Methylthio)-6,7-dihydro-5H-pyrrolo[3,4-D]pyrimidineHCID 866958504-Bromo-N-(3-(trifluoromethyl)phenyl)picolinamide

Product 1

HCID 866958544-(2-Methylsulfanyl-5,7-dihydro-pyrrolo[3,4-d]pyrimidin-6-yl)-pyridine-2-carboxylic acid (3-trifluoromethyl-phenyl)-amideYield 44.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a toluene (5 mL) solution of 4-Bromo-N-(3-(trifluoromethyl)phenyl)picolinamide (172 mg, 0.50 mmol) and 2-(Methylthio)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine (84 mg, 0.50 mmol) was added cesium carbonate (325 mg, 1.00 mmol). The mixture was purged with nitrogen and then (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (31 mg, 0.05 mmol) and palladium(II) acetate (11 mg, 0.05 mmol) were added. The reaction was capped and heated at 100° C. for 7 hours. The cooled mixture was filtered. The solid was rinsed twice with ethyl acetate then with chloroform:methanol (9:1). The combined filtrate was evaporated in vacuo. The solid was triturated with hexanes:ethyl acetate (1:1) followed by ethyl acetate:methanol (9:1) and gave the title compound (96 mg). The filtrate was chromatographed on silica gel (12 g) eluted with hexanes:ethyl acetate (1:1) and gave additional title compound (25 mg). The total amount of the title compound obtained was 120 mg (0.28 mmol, yield 56%).

Workup

  1. customThe mixture was purged with nitrogen
  2. customThe reaction was capped
  3. filtrationThe cooled mixture was filtered
  4. washThe solid was rinsed twice with ethyl acetate
  5. customThe combined filtrate was evaporated in vacuo
  6. customThe solid was triturated with hexanes:ethyl acetate (1:1)

Sources & evidence

ORD record
ord-560ae92663744dd193afbee952077e51
Source dataset
uspto-grants-2016_07
Patent number
US09388176B2

Reaction notes

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