Tri-o-tolylphosphine → (E)-7-{2-[Methyl-(3-methylbenzofuran-2-ylmethyl)carbamoyl]vinyl}-1,2,3,5-tetrahydro-pyrido[2,3-e][1,4]diazepine-4-carboxylic acid tert-butyl ester

HRID 1879971노트

반응식

HRID 1879971 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:14][C:13]2[CH:15]=[C:16](Br)[CH:17]=[N:18][C:12]=2[NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:20][N:21]([CH2:26][C:27]1[O:28][C:29]2[CH:36]=[CH:35][CH:34]=[CH:33][C:30]=2[C:31]=1[CH3:32])[C:22](=[O:25])[CH:23]=[CH2:24].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CN(C=O)C.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:1]([O:5][C:6]([N:8]1[CH2:14][C:13]2[CH:15]=[C:16](/[CH:24]=[CH:23]/[C:22](=[O:25])[N:21]([CH3:20])[CH2:26][C:27]3[O:28][C:29]4[CH:36]=[CH:35][CH:34]=[CH:33][C:30]=4[C:31]=3[CH3:32])[CH:17]=[N:18][C:12]=2[NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

9

반응물 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 57742103N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamideHCID 593328327-Bromo-1,2,3,5-tetrahydro-pyrido[2,3-e][1,4]diazepine-4-carboxylic acid tert-butyl ester

생성물 1

HCID 24891455(E)-7-{2-[Methyl-(3-methylbenzofuran-2-ylmethyl)carbamoyl]vinyl}-1,2,3,5-tetrahydro-pyrido[2,3-e][1,4]diazepine-4-carboxylic acid tert-butyl ester수율 63%

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매HCID 7854Propionitrile용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of 7-bromo-1,2,3,5-tetrahydro-pyrido[2,3-e][1,4]diazepine-4-carboxylic acid tert-butyl ester (0.53 g, 1.6 mmol) and N-methyl-N-(3-methylbenzofuran-2-ylmethyl)acrylamide (0.41 g, 1.8 mmol) in propionitrile (8.0 mL) and DMF (2.0 mL) was de-oxygenated with Ar for 10 min. The mixture was treated with (i-Pr)2EtN (0.62 mL, 3.5 mmol) and was de-oxygenated with Ar for 5 min. Pd(OAc)2 (36 mg, 0.16 mmol) and P(o-tol)3 (100 mg, 0.33 mmol) were added simultaneously, and the mixture was de-oxygenated a third time for 10 min. The mixture was heated to reflux for 6 h, then allowed to cool. The mixture was diluted with EtOAc (100 mL) and washed with H2O (50 mL). The organic layer was dried over Na2SO4, filtered and concentrated to an orange oil. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 98:2) gave the title compound (0.48 g, 62%) as a white powder and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 8.15-8.10 (m, 1H), 7.87-7.74 (m, 1H), 7.57-7.42 (m, 3H), 7.32-6.77 (m, 4H), 4.97-4.78 (m, 2H), 4.51-4.42 (m, 2H), 3.59-3.57 (m, 2H), 3.43-3.41 (m, 2H), 3.17-2.92 (m, 3H), 2.26 (s, 3H), 1.38-1.24 (m, 9H); MS (ESI) m/e 477 (M+H)+.

후처리

  1. customfor 10 min
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 6 h
  4. temperatureto cool
  5. washwashed with H2O (50 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to an orange oil
  9. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 98:2)

출처 및 근거

ORD 기록
ord-be008058cf90447e9708683469969583
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08318720B2

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