Potassium Carbonate → ethyl 8-carbamoyl-5-(2,6-difluorophenyl)-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate

HRID 1811087노트

반응식

HRID 1811087 반응식
Br[C:2]1[CH:14]=[CH:13][C:12]([C:15](=[O:17])[NH2:16])=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH:7]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:8][C:9]=1[NH:10]2.[F:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:25]=1B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.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]>[C:15]([C:12]1[CH:13]=[CH:14][C:2]([C:25]2[C:24]([F:23])=[CH:29][CH:28]=[CH:27][C:26]=2[F:30])=[C:3]2[C:11]=1[NH:10][C:9]1[CH2:8][CH:7]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:6][CH2:5][C:4]2=1)(=[O:17])[NH2:16]

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 27343362,6-Difluorophenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 59375013ethyl 5-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate2회

생성물 1

HCID 46834100ethyl 8-carbamoyl-5-(2,6-difluorophenyl)-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate수율 45.6%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8028Tetrahydrofuran용매

실험 절차

A mixture of ethyl 5-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate (Intermediate 47-1, 20 mg, 0.055 mmol), 2,6-difluorophenylboronic acid (17.3 mg, 0.110 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (4.5 mg, 11.0 mmol), potassium carbonate (15.1 mg, 0.110 mmol) and tris(dibenzylideneacetone)dipalladium (5.0 mg, 0.005 mmol) in THF (2 mL) was purged with nitrogen for 2 min, then was heated in a sealed tube overnight. The mixture was filtered and concentrated, and the residue was purified by preparative HPLC. The appropriate effluent fractions were made basic with 1 M aqueous sodium hydroxide and extracted twice with DCM. The combined organic phases were washed with water, dried and concentrated to provide ethyl 8-carbamoyl-5-(2,6-difluorophenyl)-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate as a light yellow solid (10 mg, 44%). 1H NMR (400 MHz, chloroform-d) δ 10.10 (1H, br. s.), 7.31-7.44 (2H, m), 6.95-7.06 (3H, m), 4.10-4.22 (2H, m), 2.96-3.12 (2H, m), 2.80 (1H, dddd, J=17.52, 5.99, 3.08, 2.86 Hz), 2.27-2.41 (1H, m), 2.15-2.27 (1H, m), 2.04-2.14 (1H, m), 1.69-1.85 (1H, m), 1.26 (3H, t, J=7.25 Hz). Mass spectrum m/z 399.1 (M+H)+.

후처리

  1. customwas purged with nitrogen for 2 min
  2. temperaturewas heated in a sealed tube overnight
  3. filtrationThe mixture was filtered
  4. concentrationconcentrated
  5. customthe residue was purified by preparative HPLC
  6. extractionextracted twice with DCM
  7. washThe combined organic phases were washed with water
  8. customdried
  9. concentrationconcentrated

출처 및 근거

ORD 기록
ord-7cd5e3bc93b6456ba02ab68df5888fae
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08362065B2

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