Cesium carbonate → 7-(3-(trifluoromethyl)pyridin-2-yl)-5,6,7,8-tetrahydro-N-(4-(trifluoromethylsulfonyl)phenyl)pyrido[3,4-d]pyrimidin-4-amine

HRID 971266Notes

Reaction equation

HRID 971266 reaction equation
Cl[C:2]1[C:3]2[CH2:11][CH2:10][N:9]([C:12]3[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:15]=[CH:14][N:13]=3)[CH2:8][C:4]=2[N:5]=[CH:6][N:7]=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.[F:70][C:71]([F:83])([F:82])[S:72]([C:75]1[CH:80]=[CH:79][C:78]([NH2:81])=[CH:77][CH:76]=1)(=[O:74])=[O:73]>O1CCOCC1.C(OCC)(=O)C>[F:19][C:18]([F:21])([F:20])[C:17]1[C:12]([N:9]2[CH2:10][CH2:11][C:3]3[C:2]([NH:81][C:78]4[CH:79]=[CH:80][C:75]([S:72]([C:71]([F:83])([F:70])[F:82])(=[O:74])=[O:73])=[CH:76][CH:77]=4)=[N:7][CH:6]=[N:5][C:4]=3[CH2:8]2)=[N:13][CH:14]=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 1363154-Aminophenyl trifluoromethyl sulphoneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 590214814-Chloro-7-(3-(trifluoromethyl)pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine

Product 1

HCID 120041317-(3-(trifluoromethyl)pyridin-2-yl)-5,6,7,8-tetrahydro-N-(4-(trifluoromethylsulfonyl)phenyl)pyrido[3,4-d]pyrimidin-4-amineYield 55%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Procedure

A mixture of 4-chloro-7-(3-(trifluoromethyl)pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine (0.100 g, 0.000314 mol) tris(dibenzylideneacetone)dipalladium(0) (0.058 g, 0.000063 mol), Cesium Carbonate (0.311 g, 0.000944 mol) and Xantphos (0.018 g, 0.000031 mol) in 1,4-Dioxane (3 mL, 0.04 mol) was stirred at room temperature for 10 minutes in a 5 mL microwave vial. 4-(trifluoromethylsulfonyl)benzenamine (0.15 g, 0.00063 mol) was then added as a solution in dioxane (0.5 mL) and the mixture was stirred for an additional 5 minutes. The mixture was heated via microwave in a sealed tube at 140° C. for 30 minutes, allowed to cool, and reduced in vacuo. The resulting black solid was taken up in ethyl acetate (50 mL) and washed with brine and water (2×50 mL), dried over magnesium sulfate, and reduced in vacuo. The mixture was purified by flash chromatography using an ethyl acetate:hexanes (0-100%) gradient. The combined pure fractions were reduced in vacuo to yield the desired product as a tan solid (0.087 g).

Workup

  1. stirringthe mixture was stirred for an additional 5 minutes
  2. temperatureThe mixture was heated via microwave in a sealed tube at 140° C. for 30 minutes
  3. temperatureto cool
  4. washwashed with brine and water (2×50 mL)
  5. dry with materialdried over magnesium sulfate
  6. customThe mixture was purified by flash chromatography

Sources & evidence

ORD record
ord-c16f8c114a204532b6f1de56352208e2
Source dataset
uspto-grants-2007_12
Patent number
US07312330B2

Reaction notes

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