Potassium Carbonate → 5-[4-(1-Hydroxy-1-methylethyl)phenyl]-2-({6-[(2-hydroxy-2-methylpropoxy)methyl]pyridin-2-yl}amino)thiophene-3-carboxamide

HRID 385851Notes

Reaction equation

HRID 385851 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][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>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].CCO>[OH:19][C:16]([C:13]1[CH:14]=[CH:15][C:10]([C:4]2[S:3][C:2]([NH:1][C:21]3[CH:22]=[CH:23][CH:24]=[C:25]([CH2:27][O:28][CH2:29][C:30]([OH:32])([CH3:31])[CH3:33])[N:26]=3)=[C:6]([C:7]([NH2:9])=[O:8])[CH:5]=2)=[CH:11][CH:12]=1)([CH3:17])[CH3:18]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 583352721-[(6-Bromopyridin-2-yl)methoxy]-2-methylpropan-2-olHCID 595262122-Amino-5-[4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide

Product 1

HCID 595263105-[4-(1-Hydroxy-1-methylethyl)phenyl]-2-({6-[(2-hydroxy-2-methylpropoxy)methyl]pyridin-2-yl}amino)thiophene-3-carboxamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

2-Amino-5-[4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide (0.1 g, 0.362 mmol), 1-[(6-bromopyridin-2-yl)methoxy]-2-methylpropan-2-ol (Example 217 Step 1) (0.085 g, 0.326 mmol), Pd2dba3 (0.017 g, 0.018 mmol), K2CO3 (0.055 g, 0.398 mmol) and X-Phos (0.043 g, 0.090 mmol) were added to a 5 mL microwave vial. Degassed EtOH (1 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—CHCl3) gave the title compound as a beige solid after triturating in EtOAc.

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—CHCl3)

Sources & evidence

ORD record
ord-1e0f0d0bc25a4bd48dbce20ad2bd3778
Source dataset
uspto-grants-2013_02
Patent number
US08367706B2

Reaction notes

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