Ethyl orthoformate → 3-((3S,9aS)-8-(2-(2-(1H-tetrazol-1-yl)pyrimidin-5-yl)-2,2-difluoroacetyl)octahydropyrazino[2,1-c][1,4]oxazin-3-yl)-6-fluoro-2-methylbenzonitrile

HRID 1502179노트

반응식

HRID 1502179 반응식
FC(F)(F)C(O[Si](C)(C)C)=O.[NH2:12][C:13]1[N:18]=[CH:17][C:16]([C:19]([F:43])([F:42])[C:20]([N:22]2[CH2:31][CH2:30][N:29]3[C@H:24]([CH2:25][O:26][C@@H:27]([C:32]4[C:33]([CH3:41])=[C:34]([C:37]([F:40])=[CH:38][CH:39]=4)[C:35]#[N:36])[CH2:28]3)[CH2:23]2)=[O:21])=[CH:15][N:14]=1.[CH:44](OCC)(OCC)OCC.[N:54]([Si](C)(C)C)=[N+:55]=[N-:56]>C(OCC)(=O)C.CO>[N:12]1([C:13]2[N:14]=[CH:15][C:16]([C:19]([F:43])([F:42])[C:20]([N:22]3[CH2:31][CH2:30][N:29]4[C@H:24]([CH2:25][O:26][C@@H:27]([C:32]5[C:33]([CH3:41])=[C:34]([C:37]([F:40])=[CH:38][CH:39]=5)[C:35]#[N:36])[CH2:28]4)[CH2:23]3)=[O:21])=[CH:17][N:18]=2)[CH:44]=[N:54][N:55]=[N:56]1

참가 물질

7

반응물 4

HCID 31214Ethyl orthoformateHCID 67863Acetic acid, 2,2,2-trifluoro-, trimethylsilyl esterHCID 78378AzidotrimethylsilaneHCID 1176902733-((3S,9aS)-8-(2-(2-aminopyrimidin-5-yl)-2,2-difluoroacetyl)octahydropyrazino[2,1-c][1,4]oxazin-3-yl)-6-fluoro-2-methylbenzonitrile

생성물 1

HCID 716038553-((3S,9aS)-8-(2-(2-(1H-tetrazol-1-yl)pyrimidin-5-yl)-2,2-difluoroacetyl)octahydropyrazino[2,1-c][1,4]oxazin-3-yl)-6-fluoro-2-methylbenzonitrile

시약·촉매·용매 2

HCID 887Methanol용매HCID 8857Ethyl Acetate용매

실험 절차

Trimethylsilyl trifluoroacetate (23.8 μL, 0.137 mmol) was added to a suspension of 3-((3S,9aS)-8-(2-(2-aminopyrimidin-5-yl)-2,2-difluoroacetyl)octahydropyrazino[2,1-c][1,4]oxazin-3-yl)-6-fluoro-2-methylbenzonitrile (36.1 mg, 0.081 mmol) in ethyl acetate (735 μL). The mixture was stirred for 5 min at room temperature and triethyl orthoformate (23.67 μL, 0.142 mmol) was added. After stirring for 5 more min at room temperature, azidotrimethylsilane (16.91 μL, 0.129 mmol) was added. The mixture was stirred at room temperature overnight. The reaction mixture was diluted with methanol and purified on mass-directed preparative HPLC. Appropriate fractions were collected and solvent was removed under reduced pressure. The residue was converted to hydrochloric acid salt. LC/MS: [(M+1)]+=500.0; 1H NMR (500 MHz, DMSO-d6) δ 10.33 (s, 1H), 9.35 (s, 2H), 7.85-7.94 (m, 1H), 7.43-7.54 (m, 1H), 5.14-5.27 (m, 1H), 4.01-4.60 (m, 5H), 3.13-3.95 (m, 6H), 2.53 (s, 3H).

후처리

  1. stirringAfter stirring for 5 more min at room temperature
  2. stirringThe mixture was stirred at room temperature overnight
  3. custompurified on mass-directed preparative HPLC
  4. customAppropriate fractions were collected
  5. customsolvent was removed under reduced pressure

출처 및 근거

ORD 기록
ord-437fe99024d14f0bb976f112a9cc4662
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206199B2

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