Ethyl Acetate → 3-[4-Methyl-3-oxo-7-(1-trifluoromethyl-vinyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl ester

HRID 519086노트

반응식

HRID 519086 반응식
C([O-])([O-])=O.[K+].[K+].[C:7]([O:11][C:12]([N:14]1[CH2:17][CH:16]([NH:18][C:19]2[CH:20]=[C:21]3[C:30](=[CH:31][C:32]=2Br)[O:29][CH2:28][C:27]2[N:22]3[CH:23]([CH3:35])[C:24](=[O:34])[NH:25][N:26]=2)[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].CC1(C)CC(C)OB([C:44]([C:46]([F:49])([F:48])[F:47])=[CH2:45])O1.CCOC(C)=O>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:7]([O:11][C:12]([N:14]1[CH2:17][CH:16]([NH:18][C:19]2[CH:20]=[C:21]3[C:30](=[CH:31][C:32]=2[C:44]([C:46]([F:49])([F:48])[F:47])=[CH2:45])[O:29][CH2:28][C:27]2[N:22]3[CH:23]([CH3:35])[C:24](=[O:34])[NH:25][N:26]=2)[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]

참가 물질

8

반응물 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 164142704,4,6-Trimethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1,3,2-dioxaborinaneHCID 867272933-(7-Bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 867274573-[4-Methyl-3-oxo-7-(1-trifluoromethyl-vinyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl ester수율 68%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매2회HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
80 °C

실험 절차

A mixture of K2CO3 (0.12 g, 0.86 mmol), Pd(PPh3)4 (0.099 g, 0.086 mmol), 3-(7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester ((Example 1, Step B, 0.20 g, 0.43 mmol) and 4,4,6-trimethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1,3,2-dioxaborinane (0.38 g, 1.7 mmol) in DME (15 mL) and water (2.5 mL) was stirred at 80° C. overnight. The reaction mixture was cooled to ambient temperature. EtOAc (50 mL) and water (30 mL) were added and the organic portion was separated, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by preparative TLC (eluting with 50% EtOAc in petroleum ether) to give 3-[4-methyl-3-oxo-7-(1-trifluoromethyl-vinyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl ester (0.14 g, 68%). 1H NMR (CDCl3, 400 MHz): δ 8.14 (brs, 1H), 6.83 (s, 1H), 6.28 (s, 1H), 5.92 (s, 1H), 5.73 (s, 1H), 4.66 (q, J=6.8 Hz, 1H), 4.56 (d, J=12.8 Hz, 2H), 4.26 (m, 2H), 4.16 (m, 1H), 4.04 (m, 1H), 3.70 (m, 2H), 1.53 (t, J=6.8 Hz, 3H), 1.48 (s, 9H).

후처리

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customthe organic portion was separated
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative TLC (eluting with 50% EtOAc in petroleum ether)

출처 및 근거

ORD 기록
ord-6941dcfe1010437ca0411915620039c8
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115151B2

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