2-Methyl-2-butanol → HCID 59525741, compound

HRID 386084Notes

Reaction equation

HRID 386084 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([OH:19])([CH3:18])[CH3:17])=[CH:12][C:11]=2[F:20])=[CH:5][C:6]=1[C:7]([NH2:9])=[O:8].Cl[C:22]1[CH:27]=[CH:26][N:25]=[C:24]([CH2:28][N:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)[N:23]=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]>[F:20][C:11]1[CH:12]=[C:13]([C:16]([OH:19])([CH3:17])[CH3:18])[CH:14]=[CH:15][C:10]=1[C:4]1[S:3][C:2]([NH:1][C:26]2[CH:27]=[CH:22][N:23]=[C:24]([CH2:28][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[N:25]=2)=[C:6]([C:7]([NH2:9])=[O:8])[CH:5]=1

Participants

7

Reactant 5

HCID 64052-Methyl-2-butanolHCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 582166382-Amino-5-[2-fluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamideHCID 59526018HCID 59526018, compound

Product 1

HCID 59525741HCID 59525741, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

2-Amino-5-[2-fluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide (100 mg, 0.34 mmol), 4-[(4-chloropyrimidin-2-yl)methyl]morpholine (72.6 mg, 0.34 mmol), Pd2 dba3 (31.1 mg, 0.03 mmol), K2CO3 (51.6 mg, 0.37 mmol) and X-Phos (81 mg, 0.17 mmol) were combined in a 2 mL microwave vial. Degassed tert-amyl alcohol (0.7 mL) was added and the vial evacuated and back-filled with N2 (3×). The resulting mixture was stirred at 100° C. for 24 hours. The reaction mixture was cooled to room temperature, MeOH was added and the reaction mixture was filtered through Celite. The filtrate was combined with silica gel and concentrated in vacuo. Purification of the residue by silica gel chromatography (0-20% MeOH-EtOAc) gave the title compound as a pale yellow solid.

Workup

  1. customthe vial evacuated
  2. additionback-filled with N2 (3×)
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additionMeOH was added
  5. filtrationthe reaction mixture was filtered through Celite
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by silica gel chromatography (0-20% MeOH-EtOAc)

Sources & evidence

ORD record
ord-66c78cc0461a4d1085fdf62db337b44c
Source dataset
uspto-grants-2013_02
Patent number
US08367706B2

Reaction notes

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