Boronic Acid → (3-Amino-2,6-difluoro-phenyl)-[5-(4-chlorophenyl)-1-(2,6-dichlorobenzoyl)pyrrolo[2,3-b]pyridin-3-yl]methanone

HRID 1747257Notes

Reaction equation

HRID 1747257 reaction equation
[NH2:1][C:2]1[C:3]([F:31])=[C:4]([C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17](Br)[CH:18]=3)[N:13]([C:21](=[O:30])[C:22]3[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:29])[CH:12]=2)=[O:10])[C:5]([F:8])=[CH:6][CH:7]=1.B(O)O.C(=O)(O)[O-].[Na+]>C1(P([Pd-](Cl)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[NH2:1][C:2]1[C:3]([F:31])=[C:4]([C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:24]4[CH:23]=[CH:22][C:27]([Cl:28])=[CH:26][CH:25]=4)[CH:18]=3)[N:13]([C:21](=[O:30])[C:22]3[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=3[Cl:29])[CH:12]=2)=[O:10])[C:5]([F:8])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 61668Boronic AcidHCID 516892Sodium BicarbonateHCID 72549401(3-(3-Amino-2,6-difluorobenzoyl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-1-yl)(2,6-dichlorophenyl)methanone

Product 1

HCID 72549402(3-Amino-2,6-difluoro-phenyl)-[5-(4-chlorophenyl)-1-(2,6-dichlorobenzoyl)pyrrolo[2,3-b]pyridin-3-yl]methanoneYield 201.6%

Reagents, catalysts & solvents 2

HCID 178479804HCID 178479804, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
72.5 °C

Procedure

Compound 5 (900 g; 1.7 mol) compound 6 (375.8 g; 1.4 mol), sodium bicarbonate (302.6 g; 2.1 mol) followed by 3-methyl-THF (9 L) and water (4.5 L) were added to the 20 L reactor and the mixture was purged with nitrogen at least for 1 h. Bis-triphenylphospino-palladium (II) chloride (60.8 g; 0.086 mol) was added and the reaction mixture was heated to 70-75° C. and stirred for 2 h. The reaction mixture was cooled and filtered over celite pad. The organic layer of the filtrate was separated, washed with water, and concentrated under vacuum. The precipitated solid was isolated by filtration and dried to provide compound 7 (953.9 g) as a brown solid (Purity=95.1%; Yield=˜100%). 1H NMR (DMSO-d6): δ (ppm) 8.75-8.76 (d, J=2.2 Hz, 1H), 8.59 (m, 1H), 8.52 (s, 1H), 7.80-7.82 (d, J=8.6 Hz, 1H), 7.69-7.71 (m, 3H), 7.54-7.56 (d, J=8.6 Hz, 2H), 6.99-7.07 (m, 2H), and 5.36 (s, 2H). MS (ESI) [M+H+]+=556.1 and 558.1.

Workup

  1. additionwere added to the 20 L reactor
  2. customthe mixture was purged with nitrogen at least for 1 h
  3. temperatureThe reaction mixture was cooled
  4. filtrationfiltered over celite pad
  5. customThe organic layer of the filtrate was separated
  6. washwashed with water
  7. concentrationconcentrated under vacuum
  8. customThe precipitated solid was isolated by filtration
  9. customdried

Sources & evidence

ORD record
ord-af2b7ac0e8b149a78fe2e9a11c5deaba
Source dataset
uspto-grants-2015_10
Patent number
US09150570B2

Reaction notes

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