2-Methyl-2-butanol → 2-({6-[(2-Hydroxy-2-methylpropoxy)methyl]pyridin-2-yl}amino)-5-[4-(methylsulfonyl)phenyl]thiophene-3-carboxamide

HRID 385850Notes

Reaction equation

HRID 385850 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:10]2[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=2)=[CH:5][C:6]=1[C:7]([NH2:9])=[O:8].Br[C:21]1[N:26]=[C:25]([CH2:27][O:28][CH2:29][C:30]([CH3:33])([OH:32])[CH3:31])[CH:24]=[CH:23][CH:22]=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]>[OH:32][C:30]([CH3:33])([CH3:31])[CH2:29][O:28][CH2:27][C:25]1[N:26]=[C:21]([NH:1][C:2]2[S:3][C:4]([C:10]3[CH:11]=[CH:12][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:14][CH:15]=3)=[CH:5][C:6]=2[C:7]([NH2:9])=[O:8])[CH:22]=[CH:23][CH:24]=1

Participants

7

Reactant 5

HCID 64052-Methyl-2-butanolHCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 582564812-Amino-5-[4-(methylsulfonyl)phenyl]thiophene-3-carboxamideHCID 583352721-[(6-Bromopyridin-2-yl)methoxy]-2-methylpropan-2-ol

Product 1

HCID 595257222-({6-[(2-Hydroxy-2-methylpropoxy)methyl]pyridin-2-yl}amino)-5-[4-(methylsulfonyl)phenyl]thiophene-3-carboxamide

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

2-Amino-5-[4-(methylsulfonyl)phenyl]thiophene-3-carboxamide (150 mg, 0.51 mmol), 1-[(6-bromopyridin-2-yl)methoxy]-2-methylpropan-2-ol (Example 217 Step 1) (125 mg, 0.48 mmol), Pd2 dba3 (46.3 mg, 0.051 mmol), K2CO3 (77 mg, 0.557 mmol) and X-Phos (120 mg, 0.25 mmol) were added to a 5 mL microwave vial. Degassed tert-amyl alcohol (1.2 mL) was added and the vial evacuated and back-filled with N2 (3×). The resulting mixture was stirred at 100° C. overnight. After cooling to room temperature, the mixture was diluted with methanol, silica gel was added, and the solvent was removed in vacuo. Purification of the residue by flash chromatography (silica, 0-10% MeOH-DCM) gave the title compound as a yellow solid.

Workup

  1. customthe vial evacuated
  2. additionback-filled with N2 (3×)
  3. temperatureAfter cooling to room temperature
  4. additionthe mixture was diluted with methanol, silica gel
  5. additionwas added
  6. customthe solvent was removed in vacuo
  7. customPurification of the residue by flash chromatography (silica, 0-10% MeOH-DCM)

Sources & evidence

ORD record
ord-4046905124d546f29a50d2208ae64d3a
Source dataset
uspto-grants-2013_02
Patent number
US08367706B2

Reaction notes

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