Tetrahydrofurfuryl alcohol → N2-[(S)-1-(4-Fluorophenyl)ethyl]-N4-(pyrazin-2-yl)-6-[(tetrahydrofuran-2-yl)methoxy]pyrimidine-2,4-diamine

HRID 1187716Notes

Reaction equation

HRID 1187716 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[CH3:10])[N:5]=[C:4]([NH:18][C:19]2[CH:24]=[N:23][CH:22]=[CH:21][N:20]=2)[CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[CH2:67]([OH:73])[CH:68]1[O:72][CH2:71][CH2:70][CH2:69]1>O1CCOCC1>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C@@H:9]([NH:8][C:6]2[N:5]=[C:4]([NH:18][C:19]3[CH:24]=[N:23][CH:22]=[CH:21][N:20]=3)[CH:3]=[C:2]([O:73][CH2:67][CH:68]3[CH2:69][CH2:70][CH2:71][O:72]3)[N:7]=2)[CH3:10])=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 7360Tetrahydrofurfuryl alcoholHCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86659380(S)-6-Chloro-N2-[1-(4-fluorophenyl)ethyl]-N4-(pyrazin-2-yl)pyrimidine-2,4-diamine

Product 1

HCID 56838235N2-[(S)-1-(4-Fluorophenyl)ethyl]-N4-(pyrazin-2-yl)-6-[(tetrahydrofuran-2-yl)methoxy]pyrimidine-2,4-diamine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To 200 mg of (S)-6-chloro-N2-[1-(4-fluorophenyl)ethyl]-N4-(pyrazin-2-yl)pyrimidine-2,4-diamine, 246 mg of tripotassium phosphate, 111 mg of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl and 60 mg of tris(dibenzylideneacetone)(chloroform)dipalladium, 4 ml of tetrahydrofurfurylalcohol and 2 ml of 1,4-dioxane were added, and the mixture was subjected to degassing, and substituted by argon gas, and then was stirred at 100° C. for 1 hour. The reaction solution was diluted with ethyl acetate and was washed in turn with water and brine and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and then the obtained residue was purified by silica gel column chromatography to obtain 77 mg of the objective compound as pale yellow powder.

Workup

  1. customto degassing
  2. additionThe reaction solution was diluted with ethyl acetate
  3. washwas washed in turn with water and brine
  4. dry with materialdried over magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-c8c2edf4f9234384bf16be4b8011f6b7
Source dataset
uspto-grants-2014_03
Patent number
US08673891B2

Reaction notes

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