2-Methyl-2-butanol → HCID 59525788, compound

HRID 386093Notes

Reaction equation

HRID 386093 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:10]2[C:15]([F:16])=[CH:14][C:13]([C:17]([OH:20])([CH3:19])[CH3:18])=[CH:12][C:11]=2[F:21])=[CH:5][C:6]=1[C:7]([NH2:9])=[O:8].[CH3:22][NH:23][C:24](=[O:34])[O:25][CH2:26][C:27]1[N:32]=[C:31](Cl)[CH:30]=[CH:29][N:28]=1.C([O-])([O-])=O.[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(O)(CC)(C)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]>[CH3:22][NH:23][C:24](=[O:34])[O:25][CH2:26][C:27]1[N:28]=[C:29]([NH:1][C:2]2[S:3][C:4]([C:10]3[C:11]([F:21])=[CH:12][C:13]([C:17]([OH:20])([CH3:18])[CH3:19])=[CH:14][C:15]=3[F:16])=[CH:5][C:6]=2[C:7]([NH2:9])=[O:8])[CH:30]=[CH:31][N:32]=1

Participants

7

Reactant 5

HCID 64052-Methyl-2-butanolHCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 595256192-Amino-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamideHCID 59526076HCID 59526076, compound

Product 1

HCID 59525788HCID 59525788, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

2-Amino-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide (85 mg, 0.272 mmol), (4-chloropyrimidin-2-yl)methyl methylcarbamate (54.9 mg, 0.272 mmol), Pd2 dba3 (24.92 mg, 0.027 mmol), K2CO3 (41.4 mg, 0.299 mmol) and X-Phos (64.9 mg, 0.136 mmol) were added to a 5 mL microwave vial. Degassed tert-amyl alcohol (0.6 mL) was added and the vial evacuated and back-filled with N2 (3×). The resulting mixture was stirred at 100° C. overnight. The reaction mixture was cooled to room temperature, MeOH and silica gel were added, and the solvent was removed in vacuo. Purification of the residue twice by silica gel chromatography (0-10% MeOH-DCM) gave [4-({3-(aminocarbonyl)-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-thienyl}amino)pyrimidin-2-yl]methyl methylcarbamate as a beige solid after triturating in DCM.

Workup

  1. customthe vial evacuated
  2. additionback-filled with N2 (3×)
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additionMeOH and silica gel were added
  5. customthe solvent was removed in vacuo
  6. customPurification of the residue twice by silica gel chromatography (0-10% MeOH-DCM)

Sources & evidence

ORD record
ord-972f4e2ae8144364b1fafb59766cc7c3
Source dataset
uspto-grants-2013_02
Patent number
US08367706B2

Reaction notes

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