Potassium Phosphate, Tribasic → HCID 71247820, compound

HRID 2171915Notes

Reaction equation

HRID 2171915 reaction equation
[C:1]1([CH3:32])[CH:6]=[CH:5][C:4]([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=[C:13]3[C:12](B3OC(C)(C)C(C)(C)O3)=[CH:11]2)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[C:33]([N:37]([CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49])[NH:38][C:39]1[C:44]([F:45])=[CH:43][N:42]=[C:41](Cl)[N:40]=1)([CH3:36])([CH3:35])[CH3:34].[O-]P([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>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>[C:33]([N:37]([CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49])[NH:38][C:39]1[C:44]([F:45])=[CH:43][N:42]=[C:41]([C:12]2[C:13]3[C:14](=[N:15][CH:16]=[C:17]([C:19]([F:20])([F:22])[F:21])[CH:18]=3)[N:10]([S:7]([C:4]3[CH:3]=[CH:2][C:1]([CH3:32])=[CH:6][CH:5]=3)(=[O:8])=[O:9])[CH:11]=2)[N:40]=1)([CH3:36])([CH3:35])[CH3:34]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59414394HCID 59414394, compoundHCID 86714773HCID 86714773, compound2×

Product 1

HCID 71247820HCID 71247820, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)pyrrolo[2,3-b]pyridine, 153a, (0.551 g, 1.181 mmol), ethyl 2-(1-tert-butyl-2-(2-chloro-5-fluoropyrimidin-4-yl)hydrazinyl)ethanoate, 152a, (0.300 g, 0.984 mmol) and K3PO4 (0.627 g, 2.953 mmol) in 2-MethylTHF (26 mL) and H2O (5 mL) was degassed under a stream of nitrogen for 45 minutes. To the reaction mixture was added X-phos (0.056 g, 0.118 mmol) and Pd2(dba)3 (0.022 g, 0.025 mmol). The reaction mixture was heated at 120° C. for 75 minutes. The aqueous phase was removed and the organic phase was filtered through a pad of celite, concentrated in vacuo and purified by silica gel chromatography (30% EtOAc/Hexanes) to afford 540 mg of the desired product: 1H NMR (400 MHz, CDCl3) δ 9.49 (s, 1H), 8.71 (t, J=7.0 Hz, 1H), 8.63 (d, J=11.1 Hz, 1H), 8.16-8.11 (m, 3H), 7.31 (d, J=8.2 Hz, 2H), 7.11 (d, J=21.4 Hz, 1H), 4.10 (dd, J=13.4, 6.3 Hz, 2H), 3.79 (s, 2H), 2.39 (s, 3H), 1.24 (s, 9H), 1.17 (t, J=7.1 Hz, 3H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=4.18 minutes (M+H) 609.37.

Workup

  1. customThe aqueous phase was removed
  2. filtrationthe organic phase was filtered through a pad of celite
  3. concentrationconcentrated in vacuo
  4. custompurified by silica gel chromatography (30% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-3e29a73c072f4a52a01f1ccc72a0dfe8
Source dataset
uspto-grants-2015_06
Patent number
US09051319B2

Reaction notes

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