Potassium Phosphate, Tribasic → HCID 59244850, compound

HRID 912277Notes

Reaction equation

HRID 912277 reaction equation
[CH3:1][O:2][C:3](=[O:20])[CH2:4][N:5]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C:6]1[CH:11]=[C:10](Cl)[CH:9]=[CH:8][N:7]=1.[CH3:21][O:22][C:23]1[CH:60]=[CH:59][C:26]([CH2:27][N:28]([CH2:50][C:51]2[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][CH:52]=2)[C:29]2[N:34]=[CH:33][C:32]([C:35]3[C:36]4[CH2:49][CH2:48][NH:47][C:37]=4[N:38]=[C:39]([N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[N:40]=3)=[CH:31][N:30]=2)=[CH:25][CH:24]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[CH3:1][O:2][C:3](=[O:20])[CH2:4][N:5]([C:6]1[CH:11]=[C:10]([N:47]2[C:37]3[N:38]=[C:39]([N:41]4[CH2:42][CH2:43][O:44][CH2:45][CH2:46]4)[N:40]=[C:35]([C:32]4[CH:33]=[N:34][C:29]([N:28]([CH2:50][C:51]5[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][CH:52]=5)[CH2:27][C:26]5[CH:59]=[CH:60][C:23]([O:22][CH3:21])=[CH:24][CH:25]=5)=[N:30][CH:31]=4)[C:36]=3[CH2:49][CH2:48]2)[CH:9]=[CH:8][N:7]=1)[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14]

Participants

8

Reactant 4

HCID 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]-amineHCID 59244623HCID 59244623, compound

Product 1

HCID 59244850HCID 59244850, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A DMF solution (4 ml) of [tert-butoxycarbonyl-(4-chloro-pyridin-2-yl)-amino]-acetic acid methyl ester (200 mg, 0.667 mmol) obtained in Step A, bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (300 mg, 0.556 mmol), palladium acetate (12.5 mg, 0.0556 mmol), S-Phos (46 mg, 0.111 mmol) and potassium phosphate (354 mg, 1.67 mmol) was deaerated under irradiation of ultrasonic wave, followed by stirring at 100° C. for 1 hour under a nitrogen atmosphere. The reaction mixture was cooled to room temperature, and diluted with water, followed by extraction with dichloromethane (30 ml×2). The organic layers were combined, and washed with saturated aqueous sodium chloride solution. After the organic layer was dried over magnesium sulfate, the magnesium sulfate was filtered off, and the filtrate was concentrated under reduced pressure, followed by purification of the residue by silica gel column chromatography (dichloromethane/methanol=50:1), to obtain {[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)-pyridin-2-yl]-tert-butoxycarbonyl-amino}-acetic acid methyl ester as a yellow solid (400 mg, 90%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionfollowed by extraction with dichloromethane (30 ml×2)
  3. washwashed with saturated aqueous sodium chloride solution
  4. dry with materialAfter the organic layer was dried over magnesium sulfate
  5. filtrationthe magnesium sulfate was filtered off
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customfollowed by purification of the residue by silica gel column chromatography (dichloromethane/methanol=50:1)

Sources & evidence

ORD record
ord-5524c43dbf6c4e6c826d3913441b222b
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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