Formaldehyde → Tert-butyl 3-methyl-3-(methyl(1-methyl-2-oxo-8-(trifluoromethyl)-3-((2-(tri methylsilyl)ethoxy)methyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)amino)azetidine-1-carboxylate

HRID 519060노트

반응식

HRID 519060 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([CH3:41])([NH:12][C:13]2[CH:14]=[C:15]3[C:24](=[CH:25][C:26]=2[C:27]([F:30])([F:29])[F:28])[O:23][CH2:22][C:21]2[N:16]3[CH:17]([CH3:40])[C:18](=[O:39])[N:19]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[N:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C=O.CO.[BH3-][C:47]#N.[Na+]>CC(O)C.CC(O)=O>[CH3:41][C:10]1([N:12]([CH3:47])[C:13]2[C:26]([C:27]([F:29])([F:28])[F:30])=[CH:25][C:24]3[O:23][CH2:22][C:21]4=[N:20][N:19]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:36])([CH3:37])[CH3:38])[C:18](=[O:39])[CH:17]([CH3:40])[N:16]4[C:15]=3[CH:14]=2)[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:11]1

참가 물질

7

반응물 4

HCID 712FormaldehydeHCID 887MethanolHCID 5003444Sodium cyanoborohydrideHCID 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 ester

생성물 1

HCID 86727426Tert-butyl 3-methyl-3-(methyl(1-methyl-2-oxo-8-(trifluoromethyl)-3-((2-(tri methylsilyl)ethoxy)methyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)amino)azetidine-1-carboxylate수율 53%

시약·촉매·용매 2

HCID 176Acetic Acid용매2회HCID 3776Isopropanol용매

반응 조건

온도
110 °C

실험 절차

A mixture of 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 (Example #100, Step A, 0.250 g, 0.417 mmol) and paraformaldehyde (neat, 0.250 g, 8.34 mmol) in iPrOH (5 mL) and AcOH (0.5 ml) was stirred at 110° C. for 2 days. The reaction mixture was cooled to ambient temperature and the solvent was removed in vacuo. Then, MeOH (5 mL), AcOH (2.5 mL) and NaBH3CN (0.524 g, 8.34 mmol) were added. The mixture was stirred at 60° C. for 1 h. The reaction mixture was cooled to ambient temperature and solvent was removed in vacuo. The residue was purified by column chromatography on silica gel (eluting with 5-10% EtOAc in petroleum ether) to give tert-butyl 3-methyl-3-(methyl(1-methyl-2-oxo-8-(trifluoromethyl)-3-((2-(trimethylsilyl)ethoxy)methyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)amino)azetidine-1-carboxylate (0.135 g, 53%). 1H NMR (CDCl3, 400 MHz): δ 7.25 (s, 1H), 6.72 (s, 1H), 5.10 (m, 2H), 4.65 (m, 1H), 4.66 (q, J=13.2 Hz, 2H), 4.03 (d, J=8.8 Hz, 1H), 3.90 (d, J=12.4 Hz, 1H), 3.66 (t, 2H), 3.58 (t, 2H), 2.68 (s, 3H), 1.48 (s, 3H), 1.47 (d, J=6.4 Hz, 3H), 1.42 (s, 9H), 0.99 (m, 2H), 0.00 (s, 9H).

후처리

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customthe solvent was removed in vacuo
  3. stirringThe mixture was stirred at 60° C. for 1 h
  4. temperatureThe reaction mixture was cooled to ambient temperature
  5. customsolvent was removed in vacuo
  6. customThe residue was purified by column chromatography on silica gel (eluting with 5-10% EtOAc in petroleum ether)

출처 및 근거

ORD 기록
ord-bc209c7cac2042f9ba8e334817b9066a
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115151B2

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