Hydrochloric Acid → 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)-3-fluoro-benzoic acid

HRID 912161Notes

Reaction equation

HRID 912161 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.Br[C:42]1[CH:50]=[CH:49][C:45]([C:46]([OH:48])=[O:47])=[CH:44][C:43]=1[F:51].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl>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.CN(C)C=O>[CH3:38][O:37][C:34]1[CH:33]=[CH:32][C:31]([CH2:30][N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:40][CH:39]=2)[C:9]2[N:10]=[CH:11][C:12]([C:15]3[C:16]4[CH2:29][CH2:28][N:27]([C:42]5[CH:50]=[CH:49][C:45]([C:46]([OH:48])=[O:47])=[CH:44][C:43]=5[F:51])[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:13][N:14]=2)=[CH:36][CH:35]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 27733414-Bromo-3-fluorobenzoic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 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 592443954-(4-{2-[Bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidin-7-yl)-3-fluoro-benzoic acid

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A dimethylformamide solution (15 ml) of bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (700 mg, 1.30 mmol), 4-bromo-3-fluorobenzoic acid (341 mg, 1.56 mmol), tris(dibenzylideneacetone)dipalladium (29.7 mg, 0.0324 mmol), X-Phos (61.8 mg, 0.130 mmol) and potassium phosphate (881 mg, 4.15 mmol) was degassed under ultrasonic irradiation, followed by stirring at 100° C. for 24 hours under a nitrogen atmosphere. After the reaction mixture was cooled to room temperature, 6M hydrochloric acid (2 ml) and water (15 ml) were added, followed by stirring at room temperature for 1 hour. The precipitated solid was filtered, and ethyl acetate (15 ml) was added, followed by irradiation of ultrasonic wave. The solid was filtered, and washed with ethyl acetate, whereby 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)-3-fluoro-benzoic acid was obtained as a yellow solid (679 mg, 77%).

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. stirringby stirring at room temperature for 1 hour
  3. filtrationThe precipitated solid was filtered
  4. additionethyl acetate (15 ml) was added
  5. customfollowed by irradiation of ultrasonic wave
  6. filtrationThe solid was filtered
  7. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-fc26cf2eb49b44ee9637f75d29eb3b09
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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