Potassium Phosphate, Tribasic → HCID 86714788, compound

HRID 2171936Notes

Reaction equation

HRID 2171936 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH:9]([C:16]2([C:21]([F:24])([F:23])[F:22])[CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:5]([F:25])=[CH:4][N:3]=1.[F:26][C:27]1[CH:28]=[C:29]2[C:35](B3OC(C)(C)C(C)(C)O3)=[CH:34][N:33]([S:45]([C:48]3[CH:53]=[CH:52][C:51]([CH3:54])=[CH:50][CH:49]=3)(=[O:47])=[O:46])[C:30]2=[N:31][CH:32]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1COCC1.O.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:25][C:5]1[C:6]([NH:8][CH:9]([C:16]2([C:21]([F:24])([F:23])[F:22])[CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:7][C:2]([C:35]2[C:29]3[C:30](=[N:31][CH:32]=[C:27]([F:26])[CH:28]=3)[N:33]([S:45]([C:48]3[CH:53]=[CH:52][C:51]([CH3:54])=[CH:50][CH:49]=3)(=[O:46])=[O:47])[CH:34]=2)=[N:3][CH:4]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 672856905-fluoro-1-((4-methylphenyl)sulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo(2,3-b)pyridine2×HCID 86714787HCID 86714787, compound2×

Product 1

HCID 86714788HCID 86714788, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of racemic ethyl 3-(2-chloro-5-fluoropyrimidin-4-ylamino)-3-(1-(trifluoromethyl)cyclopentyl)propanoate, 196a, (0.084 g, 0.219 mmol) in THF (10 mL) and water (1 mL) was added 5-fluoro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine, 7a, (0.137 g, 0.328 mmol) and potassium phosphate (0.140 g, 0.657 mmol). The resulting mixture was degassed under a stream of nitrogen for 10 minutes. To the reaction was then added X-Phos (0.010 g, 0.021 mmol) and Pd2(dba)3 (0.010 g, 0.011 mmol). The reaction was irradiated for 15 minutes at 135° C. in a microwave. The resulting mixture was concentrated in vacuo to a brown oil which was purified by silica gel chromatography (EtOAc/CH2Cl2) to afford 80 mg of the desired product as a pale yellow solid: LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=4.22 minutes (M+H) 638.42.

Workup

  1. customThe resulting mixture was degassed under a stream of nitrogen for 10 minutes
  2. customThe reaction was irradiated for 15 minutes at 135° C. in a microwave
  3. concentrationThe resulting mixture was concentrated in vacuo to a brown oil which
  4. customwas purified by silica gel chromatography (EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-8bc7bf4aff7d4dbab55c7df046cff289
Source dataset
uspto-grants-2015_06
Patent number
US09051319B2

Reaction notes

Loading…