Potassium Phosphate, Tribasic → HCID 67385434, compound

HRID 912148Notes

Reaction equation

HRID 912148 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.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[C:70]([NH:74][C:75](=[O:83])[C:76]1[CH:81]=[C:80](Cl)[CH:79]=[CH:78][N:77]=1)([CH3:73])([CH3:72])[CH3:71].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:70]([NH:74][C:75]([C:76]1[CH:81]=[C:80]([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:79]=[CH:78][N:77]=1)=[O:83])([CH3:73])([CH3:71])[CH3:72]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 24850887N-tert-Butyl-4-chloropyridine-2-carboxamideHCID 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 67385434HCID 67385434, compoundYield 41%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (81 mg), palladium acetate (1.7 mg), S-Phos (6.2 mg), 4-chloropicolinic acid t-butylamide (64 mg) and potassium phosphate (64 mg) were stirred in dimethylformamide (1.5 ml) under an argon atmosphere at 100° C. for 2 days. The reaction mixture was cooled to room temperature, and subsequently diluted with water (20 ml), followed by extraction with ethyl acetate (10 ml). The organic layer was washed with brine, and dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/0 to 3/1), 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)-pyridine-2-carboxylic acid tert-butylamide as a pale yellow solid (44 mg, 41%). The above compound was dissolved in trifluoroacetic acid (3 ml), and refluxed for 5 hours in the presence of N-acetylcysteine (33 mg, 3.3 equivalents). The reaction mixture was concentrated under reduced pressure, and water (2 ml) was added to the resulting residue, followed by neutralization with saturated sodium bicarbonate water. The resulting precipitate was filtered and dried, and purified by amino silica gel column chromatography (dichloromethane), to obtain a colorless powder (17 mg, 58%).

Workup

  1. extractionfollowed by extraction with ethyl acetate (10 ml)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationAfter filtering off the drying agent
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/0 to 3/1)

Sources & evidence

ORD record
ord-a3d5bf1791b1490fb24f9d2b9c9856ca
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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