Potassium Phosphate, Tribasic → HCID 67385929, compound

HRID 912211Notes

Reaction equation

HRID 912211 reaction equation
I[C:2]1[CH:3]=[C:4]([NH:8][C:9]([N:11]2[C:15]3[N:16]=[C:17]([N:45]4[CH2:50][CH2:49][O:48][CH2:47][CH2:46]4)[N:18]=[C:19]([C:20]4[CH:21]=[N:22][C:23]([N:26]([CH2:36][C:37]5[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=5)[CH2:27][C:28]5[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=5)=[N:24][CH:25]=4)[C:14]=3[CH2:13][CH2:12]2)=[O:10])[CH:5]=[CH:6][CH:7]=1.[CH2:51]([N:53]1[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1)[CH3:52].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH2:51]([N:53]1[CH2:58][CH2:57][N:56]([C:2]2[CH:3]=[C:4]([NH:8][C:9]([N:11]3[C:15]4[N:16]=[C:17]([N:45]5[CH2:50][CH2:49][O:48][CH2:47][CH2:46]5)[N:18]=[C:19]([C:20]5[CH:21]=[N:22][C:23]([N:26]([CH2:36][C:37]6[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=6)[CH2:27][C:28]6[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=6)=[N:24][CH:25]=5)[C:14]=4[CH2:13][CH2:12]3)=[O:10])[CH:5]=[CH:6][CH:7]=2)[CH2:55][CH2:54]1)[CH3:52]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 791961-EthylpiperazineHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 59244836HCID 59244836, compound

Product 1

HCID 67385929HCID 67385929, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-{2-[Bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid (3-iodo-phenyl)-amide (48 mg) obtained in Step A, 1-ethyl-piperazine (77.5 μl), tris(dibenzylideneacetone)dipalladium (5.5 mg), S-Phos (5.0 mg) and potassium phosphate (26.0 mg) were stirred in DMF (5 ml) at 100° C. for 3 hours. To this, water was added, to filter the solid, which was dissolved in dichloromethane, followed by drying over sodium sulfate. After the sodium sulfate was filtered off, the solvent was distilled off under reduced pressure, followed by purification by silica gel column chromatography (dichloromethane/methanol=100/1 to 20/1), to obtain 4-{2-[bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid [3-(4-ethyl-piperazin-1-yl)-phenyl]-amide as a crude product. To this compound (23.1 mg), N-Acetylcysteine (10 mg) was added, followed by refluxing in TFA (1 ml) for 6 hours. TFA was distilled off, followed by purification by silica gel column chromatography (dichloromethane/2M-ammonia methanol=1/0 to 20/1), and further the resulting solid was washed with saturated sodium hydrogencarbonate aqueous solution (3 ml), water (3 ml) and acetonitrile (3 ml), to obtain the desired compound (D-81) as a yellow solid (12.5 mg, 79%).

Workup

  1. filtrationto filter the solid, which
  2. dissolutionwas dissolved in dichloromethane
  3. dry with materialby drying over sodium sulfate
  4. filtrationAfter the sodium sulfate was filtered off
  5. distillationthe solvent was distilled off under reduced pressure
  6. customfollowed by purification by silica gel column chromatography (dichloromethane/methanol=100/1 to 20/1)

Sources & evidence

ORD record
ord-a8e8dee622d34421bb84ca09c5cfc094
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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