Sodium Hydroxide → 2-Fluoro-5-(2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-benzonitrile

HRID 912136Notes

Reaction equation

HRID 912136 reaction equation
Cl[C:2]1[C:3]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[C:4]=2[N:5]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:7]=1.[C:23]([C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][C:30]=1[F:31])#[N:24].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[OH-].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)(C)(C)C>[F:31][C:30]1[CH:29]=[CH:28][C:27]([C:2]2[C:3]3[CH2:16][CH2:15][N:14]([C:17]4[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=4)[C:4]=3[N:5]=[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[N:7]=2)=[CH:26][C:25]=1[C:23]#[N:24]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 27579643-Cyano-4-fluorophenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 592447084-chloro-2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 248904442-Fluoro-5-(2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-benzonitrileYield 24.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

To 4-chloro-2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine (10 mg, 0.0315 mmol), 3-cyano-4-fluorophenylboronic acid (10.4 mg, 0.0630 mmol), palladium acetate (1.4 mg, 0.0063 mmol), S-Phos (5.2 mg, 0.0126 mmol) and sodium hydroxide (2.5 mg, 0.063 mmol), t-butanol (1 ml) was added, followed by being degassed under ultrasonic irradiation. This was stirred at 100° C. for 3 hours, followed by extraction with ethyl acetate with the addition of water, and the organic layer was washed with brine. After drying over anhydrous sodium sulfate, concentration was carried out under reduced pressure, followed by elution with 2M ammonia methanol solution through SCX resin and then concentration. Purification by preparative TLC afforded the desired compound as a colorless solid (3.1 mg, yield 12%).

Workup

  1. customby being degassed under ultrasonic irradiation
  2. extractionfollowed by extraction with ethyl acetate with the addition of water
  3. washthe organic layer was washed with brine
  4. dry with materialAfter drying over anhydrous sodium sulfate, concentration
  5. washfollowed by elution with 2M ammonia methanol solution through SCX resin
  6. concentrationconcentration
  7. customPurification by preparative TLC

Sources & evidence

ORD record
ord-8c3cc151d80a4aeda57328193d1e693d
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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