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 519086

反応式

HRID 519086 の反応式
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]

参加物

8

反応物 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

生成物 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 ester収率 68%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒2 回HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-6941dcfe1010437ca0411915620039c8
出典データセット
uspto-grants-2015_08
特許番号
US09115151B2

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