Trifluoroacetic acid → HCID 46866123, compound

HRID 2043468Notes

Reaction equation

HRID 2043468 reaction equation
C(O[C:6]([N:8]1[CH2:11][CH:10]([C:12]#[N:13])[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.ClC1[N:27]=[C:26]([NH:28][C@H:29]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)[CH3:30])[N:25]=[C:24]([NH:38][C:39]2[CH:44]=[N:43][CH:42]=[CH:41][N:40]=2)[CH:23]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>C(Cl)Cl.O1CCOCC1.C(OCC)(=O)C.C(N(CC)CC)C>[F:37][C:34]1[CH:33]=[CH:32][C:31]([C@@H:29]([NH:28][C:26]2[N:27]=[C:6]([N:8]3[CH2:9][CH:10]([C:12]#[N:13])[CH2:11]3)[CH:23]=[C:24]([NH:38][C:39]3[CH:44]=[N:43][CH:42]=[CH:41][N:40]=3)[N:25]=2)[CH3:30])=[CH:36][CH:35]=1

Participants

10

Reactant 5

HCID 6422Trifluoroacetic acidHCID 106312831-Boc-3-cyanoazetidineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 86659380(S)-6-Chloro-N2-[1-(4-fluorophenyl)ethyl]-N4-(pyrazin-2-yl)pyrimidine-2,4-diamine

Product 1

HCID 46866123HCID 46866123, compoundYield 25%

Reagents, catalysts & solvents 4

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

216 mg of 1-(t-butoxycarbonyl)-3-cyanoazetidine was dissolved in 2.5 ml of methylene chloride, and 1 ml of trifluoroacetic acid was added thereto, and the mixture was stirred at room temperature overnight. The solvent was distilled off under reduced pressure to obtain brown oil. The obtained oil was dissolved in 4 ml of degassed 1,4-dioxane, and 302 mg of triethylamine, 205 mg of (S)-6-chloro-N2-[1-(4-fluorophenyl)ethyl]-N4-(pyrazin-2-yl)pyrimidine-2,4-diamine, 57 mg of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl, 229 mg of sodium t-butoxide and 62 mg of tris(dibenzylideneacetone)(chloroform)dipalladium were added in turn, and the mixture was stirred at 90° C. for 3 hours under argon atmosphere. The reaction solution was diluted with ethyl acetate. The solution 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 58 mg of the objective compound as pale yellow powder.

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. customto obtain brown oil
  3. stirringthe mixture was stirred at 90° C. for 3 hours under argon atmosphere
  4. washThe solution was washed in turn with water and brine
  5. dry with materialdried over magnesium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-b5c08123ad2847ea89bb9f749bb49c67
Source dataset
uspto-grants-2013_11
Patent number
US08586591B2

Reaction notes

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