Nitrogen → 5-[4-(1,1-Dioxidothiomorpholin-4-yl)phenyl]-2-({6-[(2-hydroxy-2-methylpropoxy)methyl]pyridin-2-yl}amino)thiophene-3-carboxamide

HRID 385853Notes

Reaction equation

HRID 385853 reaction equation
[O:1]=[S:2]1(=[O:25])[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[S:18][C:17]([N+:19]([O-])=O)=[C:16]([C:22]([NH2:24])=[O:23])[CH:15]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.N#N.Br[C:29]1[N:34]=[C:33]([CH2:35][O:36][CH2:37][C:38]([CH3:41])([OH:40])[CH3:39])[CH:32]=[CH:31][CH:30]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[K+].[K+]>CO.[Pt].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]>[O:1]=[S:2]1(=[O:25])[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[S:18][C:17]([NH:19][C:29]4[CH:30]=[CH:31][CH:32]=[C:33]([CH2:35][O:36][CH2:37][C:38]([OH:40])([CH3:39])[CH3:41])[N:34]=4)=[C:16]([C:22]([NH2:24])=[O:23])[CH:15]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1

Participants

9

Reactant 5

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 583352721-[(6-Bromopyridin-2-yl)methoxy]-2-methylpropan-2-olHCID 595262725-[4-(1,1-Dioxidothiomorpholin-4-yl)phenyl]-2-nitrothiophene-3-carboxamide2×

Product 1

HCID 595261385-[4-(1,1-Dioxidothiomorpholin-4-yl)phenyl]-2-({6-[(2-hydroxy-2-methylpropoxy)methyl]pyridin-2-yl}amino)thiophene-3-carboxamide

Reagents, catalysts & solvents 3

HCID 23939PlatinumCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

5-[4-(1,1-Dioxidothiomorpholin-4-yl)phenyl]-2-nitrothiophene-3-carboxamide (Intermediate 16) (525 mg, 1.376 mmol) and Pt/C, doped with V (90 mg, 0.014 mmol) were stirred at room temperature overnight in degassed MeOH (5 mL) under a balloon of H2. The vial was then evacuated and back-filled with N2 (4×) and 1-[(6-bromopyridin-2-yl)methoxy]-2-methylpropan-2-ol (Example 217 Step 1) (358 mg, 1.38 mmol), Pd2dba3 (126 mg, 0.138 mmol), X-Phos (328 mg, 0.69 mmol) and K2CO3 (209 mg, 1.51 mmol) were added. The vial was evacuated and back-filled with N2 (3×) and the resulting mixture was stirred at 100° C. for 4 hours. 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 silica gel chromatography (0-6% MeOH—CHCl3) gave the title compound as a beige solid after triturating in DCM.

Workup

  1. customThe vial was then evacuated
  2. additionwere added
  3. customThe vial was evacuated
  4. additionback-filled with N2 (3×)
  5. temperatureAfter cooling to room temperature
  6. additionthe mixture was diluted with methanol, silica gel
  7. additionwas added
  8. customthe solvent was removed in vacuo
  9. customPurification of the residue by silica gel chromatography (0-6% MeOH—CHCl3)

Sources & evidence

ORD record
ord-e9894cec37e1472cbce33b0fd2a35a29
Source dataset
uspto-grants-2013_02
Patent number
US08367706B2

Reaction notes

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