Potassium Phosphate, Tribasic → HCID 67104624, compound

HRID 2239510Notes

Reaction equation

HRID 2239510 reaction equation
Cl.Br[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[N:8][C:7]([C:15]([NH2:17])=[O:16])=[C:6]2[NH:18][C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][C:20]=1[F:26].CC1(C)C(C)(C)OB([C:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C(O)CCC.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]>[NH2:17][C:15]([C:7]1[N:8]=[N:9][C:10]2[C:5]([C:6]=1[NH:18][C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][C:20]=1[F:26])=[CH:4][C:3]([C:35]1[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]=1)=[C:12]([O:13][CH3:14])[CH:11]=2)=[O:16]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 67083813HCID 67083813, compound

Product 1

HCID 67104624HCID 67104624, compoundYield 96%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 2631-ButanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-bromo-4-(2-fluoro-4-methylphenylamino)-7-methoxycinnoline-3-carboxamide hydrochloride (Example 54, 1.40 g, 3.169 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (1.47 g, 4.75 mmol), tripotassium phosphate (2.018 g, 9.51 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.260 g, 0.63 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.29 g, 0.32 mmol) in n-butanol (4.53 ml) and water (1.81 ml) was stirred under N2 (g) at 100° C. overnight. The reaction mixture was cooled, concentrated under reduced pressure and the residue purified with silica chromatography (CH2Cl2/MeOH) to give 1.54 g (96%) of a light brown solid. 1H NMR: 11.54 (s, 1H), 8.79 (s, 1H), 7.94 (s, 1H), 7.62 (s, 1H), 7.25 (m, 2H), 7.08 (m, 2H), 5.56 (s, 1H), 3.97 (s, 3H), 3.82 (m, 2H), 3.37 (m, 2H), 2.35 (s, 3H), 2.14 (m, 2H), 1.41 (s, 6H), 1.06 (s, 9H); m/z 508.

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated under reduced pressure
  3. customthe residue purified with silica chromatography (CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-83960b3ef96d4064ace3af8131e5700b
Source dataset
uspto-grants-2010_05
Patent number
US07723337B2

Reaction notes

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