Potassium Phosphate, Tribasic → 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 (4-pyridin-3-yl-phenyl)-amide

HRID 912197Notes

Reaction equation

HRID 912197 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([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:4][CH:3]=1.[N:51]1[CH:56]=[CH:55][CH:54]=[C:53](B(O)O)[CH:52]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[N:51]1[CH:56]=[CH:55][CH:54]=[C:53]([C:2]2[CH:7]=[CH:6][C:5]([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:25]=[N:24][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:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=6)=[N:22][CH:21]=5)[C:14]=4[CH2:13][CH2:12]3)=[O:10])=[CH:4][CH:3]=2)[CH:52]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27343783-Pyridinylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 592448904-{2-[Bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid (4-iodo-phenyl)-amide

Product 1

HCID 673858194-{2-[Bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid (4-pyridin-3-yl-phenyl)-amide

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 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 (4-iodo-phenyl)-amide (35 mg) obtained in Step A, pyridin-3-boronic acid (11 mg), palladium acetate (1.0 mg), S-Phos (3.7 mg) and potassium phosphate (9.5 mg) were stirred at 100° C. for 3 hours in DMF (4.5 ml). To this, water was added, and the solid was filtered, followed by purification by silica gel column chromatography (dichloromethane/methanol=100/1 to 50/1), 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 (4-pyridin-3-yl-phenyl)-amide as a crude product. To this, N-Acetylcysteine (11 mg) was added, followed by refluxing for 4 hours in TFA (1 ml). TFA was distilled off, followed by purification by silica gel column chromatography (dichloromethane/methanol=100/1 to 50/1), to obtain the desired compound (D-65) as a colorless solid (5.0 mg, 23%, deprotection method according to the above Deprotection method 3).

Workup

  1. filtrationthe solid was filtered
  2. customfollowed by purification by silica gel column chromatography (dichloromethane/methanol=100/1 to 50/1)

Sources & evidence

ORD record
ord-ec4f828739534ae1a6041dc12767b45e
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

Loading…