Dichloromethane → HCID 86654047, compound

HRID 1948065Notes

Reaction equation

HRID 1948065 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3[CH:32]=[CH:31][C:30](Br)=[C:29]4[C:25]=3[C:26](=[O:35])[N:27]([CH3:34])[CH2:28]4)[C:20]([C:36]([F:39])([F:38])[F:37])=[CH:19][N:18]=2)=[CH:12][CH:11]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].[C:40]([O:44][C:45]([N:47]1[CH2:52][CH:51]=[C:50](B2OC(C)(C)C(C)(C)O2)[CH2:49][CH2:48]1)=[O:46])([CH3:43])([CH3:42])[CH3:41].C(=O)([O-])[O-].[K+].[K+].ClCCl>[Cl-].[Na+].O.O.C(OCC)(=O)C.O1CCOCC1>[CH2:6]([O:5][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3[CH:32]=[CH:31][C:30]([C:50]4[CH2:51][CH2:52][N:47]([C:45]([O:44][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:46])[CH2:48][CH:49]=4)=[C:29]4[C:25]=3[C:26](=[O:35])[N:27]([CH3:34])[CH2:28]4)[C:20]([C:36]([F:38])([F:37])[F:39])=[CH:19][N:18]=2)=[CH:12][CH:11]=1)([O:3][CH2:1][CH3:2])=[O:8])[CH3:7]

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 58292897Diethyl [4-({4-[(7-bromo-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate

Product 1

HCID 86654047HCID 86654047, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

Diethyl[4-({4-[(7-bromo-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate (200.0 mg, 0.3183 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (Tetrahedron Letters, 2000, 44, pp 3705-3708, 147.6 mg, 0.4774 mmol), potassium carbonate (132.0 mg, 0.9548 mmol) [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (26.0 mg, 0.03183 mmol), 1,4-dioxane (1.0 mL) and water (0.25 mL) were mixed and heated in microwave at 100° C. for 30 minutes. The crude mixture was worked up with ethyl acetate, water and brine. Column chromatography was used to purify the title compound (0-3% methanol in methylene chloride). MS (ES+): m/z 731.33 (100) [MH+]; HPLC: tR=1.53 min (UPLC, Analytical).

Workup

  1. customto purify the title compound (0-3% methanol in methylene chloride)

Sources & evidence

ORD record
ord-7108013a05c449c3b93207193f25ea90
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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