Potassium Phosphate, Tribasic → bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine

HRID 912111Notes

Reaction equation

HRID 912111 reaction equation
Cl[C:2]1[C:3]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[C:4]=2[N:5]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:7]=1.[CH3:23][O:24][C:25]1[CH:56]=[CH:55][C:28]([CH2:29][N:30]([CH2:46][C:47]2[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=2)[C:31]2[N:36]=[CH:35][C:34](B3OC(C)(C)C(C)(C)O3)=[CH:33][N:32]=2)=[CH:27][CH:26]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O>[CH3:23][O:24][C:25]1[CH:26]=[CH:27][C:28]([CH2:29][N:30]([CH2:46][C:47]2[CH:48]=[CH:49][C:50]([O:53][CH3:54])=[CH:51][CH:52]=2)[C:31]2[N:36]=[CH:35][C:34]([C:2]3[C:3]4[CH2:16][CH2:15][N:14]([C:17]5[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=5)[C:4]=4[N:5]=[C:6]([N:8]4[CH2:13][CH2:12][O:11][CH2:10][CH2:9]4)[N:7]=3)=[CH:33][N:32]=2)=[CH:55][CH:56]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 592447084-chloro-2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidineHCID 67385320Bis-(4-methoxybenzyl)-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-yl]amine

Product 1

HCID 67386412bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amineYield 87%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To 4-chloro-2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine (119 mg, 0.374 mmol) obtained from Step C, bis-(4-methoxybenzyl)-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-yl]amine (207 mg, 0.449 mmol), palladium acetate (4.2 mg, 0.0187 mmol), S-Phos (15 mg, 0.0374 mmol) and potassium phosphate (159 mg, 0.748 mmol), dimethylformamide (3 ml) was added, followed by being degassed under ultrasonic irradiation. This was stirred at 100° C. for 5 hours, followed by extraction with ethyl acetate with the addition of water, and the organic layer was washed with brine. After drying over anhydrous sodium sulfate, concentration was carried out under reduced pressure, followed by purification by silica gel column chromatography (dichloromethane/methanol=100/1 to 40/1), to obtain bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (199 mg, yield 87%).

Workup

  1. customby being degassed under ultrasonic irradiation
  2. extractionfollowed by extraction with ethyl acetate with the addition of water
  3. washthe organic layer was washed with brine
  4. dry with materialAfter drying over anhydrous sodium sulfate, concentration
  5. customfollowed by purification by silica gel column chromatography (dichloromethane/methanol=100/1 to 40/1)

Sources & evidence

ORD record
ord-e48dfaa39a4044cdbb3513419a68097b
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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