1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 4-Methyl-N-(4-(2-(pyrrolidin-1-yl)ethyl)phenyl)-3-(4-(3-(trifluoromethyl)phenyl)pyrimidin-2-yl-amino)benzamide

HRID 2172676Notes

Reaction equation

HRID 2172676 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[CH3:24])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:10][CH:9]=1)=[O:6].[F:25][C:26]([F:41])([F:40])[C:27]1[CH:28]=[C:29]([C:33]2[CH:38]=[CH:37][N:36]=[C:35]([NH2:39])[N:34]=2)[CH:30]=[CH:31][CH:32]=1.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>C1COCC1.CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:24][C:23]1[CH:22]=[CH:21][C:4]([C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[CH:10][CH:9]=2)=[O:6])=[CH:3][C:2]=1[NH:39][C:35]1[N:34]=[C:33]([C:29]2[CH:30]=[CH:31][CH:32]=[C:27]([C:26]([F:41])([F:25])[F:40])[CH:28]=2)[CH:38]=[CH:37][N:36]=1

Participants

7

Reactant 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 14781534-[3-(Trifluoromethyl)phenyl]pyrimidin-2-amineHCID 684662633-Bromo-4-methyl-N-(4-(2-(pyrrolidin-1-yl)ethyl)phenyl)benzamide

Product 1

HCID 251273414-Methyl-N-(4-(2-(pyrrolidin-1-yl)ethyl)phenyl)-3-(4-(3-(trifluoromethyl)phenyl)pyrimidin-2-yl-amino)benzamide

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 3-bromo-4-methyl-N-(4-(2-(pyrrolidin-1-yl)ethyl)phenyl)benzamide (59 mg, 0.13 mmol) and 4-(3-(trifluoromethyl)phenyl)pyrimidin-2-amine (31 mg, 0.13 mmol), KOBut (22 mg, 0.2 mmol), Pd2(dba)3 (4.6 mg, 0.005 mmol) and Xantphos (4.6 mg, 0.008 mmol) in a microwave reaction vessel was suspended in 1 mL of THF. The reaction mixture was heated in a microwave at 150° C. for 90 min. After cooling, the mixture was diluted with DMF, and then filtered with a 0.45 μm microfilter. The obtained filtrate was separated by a semi-preparative HPLC. Collected product fraction was lyophilized to give pure product as a while powder. MS (ESI+) m/z 546.1 [M+H]+.

Workup

  1. customin a microwave reaction vessel
  2. temperatureAfter cooling
  3. filtrationfiltered with a 0.45 μm microfilter
  4. customThe obtained filtrate was separated by a semi-preparative HPLC
  5. customto give pure product as a while powder

Sources & evidence

ORD record
ord-348714a27ea441eb9a2e9a2b84089f65
Source dataset
uspto-grants-2015_06
Patent number
US09056837B2

Reaction notes

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