Cesium carbonate → 3-Methyl-3-[4-methyl-3-oxo-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl ester

HRID 519031노트

반응식

HRID 519031 반응식
Br[C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][C:15]=1[C:16]([F:19])([F:18])[F:17])[O:12][CH2:11][C:10]1[N:5]2[CH:6]([CH3:29])[C:7](=[O:28])[N:8]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[N:9]=1.[NH2:30][C:31]1([CH3:42])[CH2:34][N:33]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:32]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:38]([O:37][C:35]([N:33]1[CH2:34][C:31]([CH3:42])([NH:30][C:2]2[CH:3]=[C:4]3[C:13](=[CH:14][C:15]=2[C:16]([F:19])([F:18])[F:17])[O:12][CH2:11][C:10]2[N:5]3[CH:6]([CH3:29])[C:7](=[O:28])[N:8]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[N:9]=2)[CH2:32]1)=[O:36])([CH3:41])([CH3:39])[CH3:40]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 56924482tert-Butyl 3-amino-3-methylazetidine-1-carboxylateHCID 867273036-Bromo-4-methyl-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

생성물 1

HCID 867273933-Methyl-3-[4-methyl-3-oxo-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl ester수율 67.3%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매

실험 절차

A mixture of 6-bromo-4-methyl-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Example #53, Step E, 0.110 g, 0.223 mmol), tert-butyl 3-amino-3-methylazetidine-1-carboxylate (0.062 g, 0.334 mmol), Pd(OAc)2 (0.010 g, 0.045 mmol), cesium carbonate (0.109 g, 0.334 mmol) and BINAP (0.042 g, 0.067 mmol) in toluene (5 mL) was heated at reflux for 5 h. The reaction mixture was cooled to ambient temperature and filtered. The filtrate was concentrated and the residue was purified by column chromatography on silica gel (eluting with 20% EtOAc in petroleum ether) to give 3-methyl-3-[4-methyl-3-oxo-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl ester (0.090 g, 67%) as a white solid. 1H NMR (CDCl3, 400 MHz): δ 7.13 (s, 1H), 5.93 (s, 1H), 5.10 (q, J=10.4 Hz, 2H), 4.62 (d, J=12.8 Hz, 1H), 4.58 (m, 1H), 4.49 (d, J=12.8 Hz, 1H), 4.37 (s, 1H), 4.00 (m, 2H), 3.95 (m, 2H), 3.66 (t, J=8.0 Hz, 2H), 1.63 (s, 3H), 1.47 (d, J=6.8 Hz, 3H) 1.45 (s, 9H), 0.99 (m, 2H), 0.00 (s, 9H).

후처리

  1. temperaturewas heated
  2. temperatureat reflux for 5 h
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. customthe residue was purified by column chromatography on silica gel (eluting with 20% EtOAc in petroleum ether)

출처 및 근거

ORD 기록
ord-1f421a3de58349899683b9e5217d4825
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115151B2

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