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

HRID 1747257
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HRID 1747257 반응식
[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
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참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 178479804
HCID 178479804, 화합물
촉매
HCID 962Water용매

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온도
72.5 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-af2b7ac0e8b149a78fe2e9a11c5deaba
출처 데이터셋
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09150570B2

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