Methyl 4-bromobenzoate → HCID 67385823, compound

HRID 912149Notes

Reaction equation

HRID 912149 reaction equation
[CH3:1][O:2][C:3]1[CH:40]=[CH:39][C:6]([CH2:7][N:8]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[C:9]2[N:14]=[CH:13][C:12]([C:15]3[C:16]4[CH2:29][CH2:28][NH:27][C:17]=4[N:18]=[C:19]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[N:20]=3)=[CH:11][N:10]=2)=[CH:5][CH:4]=1.[CH3:41][O:42][C:43](=[O:51])[C:44]1[CH:49]=[CH:48][C:47](Br)=[CH:46][CH:45]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:41][O:42][C:43](=[O:51])[C:44]1[CH:49]=[CH:48][C:47]([N:27]2[C:17]3[N:18]=[C:19]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[N:20]=[C:15]([C:12]4[CH:11]=[N:10][C:9]([N:8]([CH2:7][C:6]5[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:40][CH:39]=5)[CH2:30][C:31]5[CH:32]=[CH:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=5)=[N:14][CH:13]=4)[C:16]=3[CH2:29][CH2:28]2)=[CH:46][CH:45]=1

Participants

8

Reactant 4

HCID 12081Methyl 4-bromobenzoateHCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 45258862Bis-(4-methoxybenzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine

Product 1

HCID 67385823HCID 67385823, compoundYield 57.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (200 mg, 0.370 mmol), 4-bromobenzoic acid methyl ester (95 mg, 0.444 mmol), palladium acetate (10.0 mg, 0.0444 mmol), S-Phos (36.4 mg, 0.0888 mmol) and potassium phosphate (157 mg, 0.740 mmol) in dimethylformamide (3 ml) was degassed under ultrasonic irradiation, and stirred at 100° C. for 3 hours. To this, water was added, and the precipitate was filtered, which was subsequently dissolved in dichloromethane, and dried over sodium sulfate, followed by concentration under reduced pressure. Purification by silica gel column chromatography (dichloromethane/methanol=200/1) afforded 4-(4-{2-[bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidin-7-yl)-benzoic acid methyl ester as a yellow powder (143.5 mg, Yield 57%).

Workup

  1. filtrationthe precipitate was filtered
  2. dissolutionwhich was subsequently dissolved in dichloromethane
  3. dry with materialdried over sodium sulfate
  4. concentrationfollowed by concentration under reduced pressure
  5. customPurification by silica gel column chromatography (dichloromethane/methanol=200/1)

Sources & evidence

ORD record
ord-c54e367bb9274121ba76c633250b54df
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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