2-Methyl-2-butanol → 5-[2,6-Difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-{[6-(2-hydroxyethyl)-5-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-2-yl]amino}thiophene-3-carboxamide

HRID 1799546Notes

Reaction equation

HRID 1799546 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].Cl[C:23]1[N:28]=[C:27]2[CH2:29][N:30]([CH2:33][CH2:34][OH:35])[C:31](=[O:32])[C:26]2=[CH:25][CH:24]=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:16][C:15]1[CH:14]=[C:13]([C:17]([OH:20])([CH3:18])[CH3:19])[CH:12]=[C:11]([F:21])[C:10]=1[C:4]1[S:3][C:2]([NH:1][C:23]2[N:28]=[C:27]3[CH2:29][N:30]([CH2:33][CH2:34][OH:35])[C:31](=[O:32])[C:26]3=[CH:25][CH:24]=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 582166462-Chloro-6-(2-hydroxyethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-oneHCID 595256192-Amino-5-[2,6-difluoro-4-(1-hydroxy-1-methylethyl)phenyl]thiophene-3-carboxamide

Product 1

HCID 445541085-[2,6-Difluoro-4-(1-hydroxy-1-methylethyl)phenyl]-2-{[6-(2-hydroxyethyl)-5-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-2-yl]amino}thiophene-3-carboxamide

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 (90 mg, 0.29 mmol), 2-chloro-6-(2-hydroxyethyl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one (61 mg, 0.29 mmol), Pd2dba3 (26.4 mg, 0.029 mmol), K2CO3 (43.8 mg, 0.317 mmol) and X-Phos (68.7 mg, 0.144 mmol) were added to a 2 mL microwave vial. Degassed tert-amyl alcohol (0.7 mL) was added and the vial evacuated and back-filled with nitrogen (3×). The resulting mixture was stirred at 100° C. overnight. Room temperature was attained, MeOH was added and the resulting mixture filtered through Celite. The filtrate was concentrated in vacuo while loading onto silica. Purification of the residue by silica gel chromatography (0-20% MeOH/EtOAc) gave the title compound as a pale yellow solid after triturating in EtOH. LRMS (APCI) calc'd for (C23H23F2N4O4S) [M+H]+, 489. found 489.

Workup

  1. customthe vial evacuated
  2. additionback-filled with nitrogen (3×)
  3. customRoom temperature
  4. additionMeOH was added
  5. filtrationthe resulting mixture filtered through Celite
  6. concentrationThe filtrate was concentrated in vacuo
  7. customPurification of the residue by silica gel chromatography (0-20% MeOH/EtOAc)

Sources & evidence

ORD record
ord-aa6a096d77c64eb4ad5b743056ee8529
Source dataset
uspto-grants-2013_01
Patent number
US08344144B2

Reaction notes

Loading…