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Triethylamine → (2S)-ethyl 2-tert-butoxy-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-((2-(trimethylsilyl)ethoxy)carbonylamino)pyrazolo[1,5-a]pyrimidin-6-yl)acetate

HRID 1468748
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HRID 1468748 반응식
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:36])=[N:14][C:15]2[N:16]([N:30]=[C:31](C(O)=O)[CH:32]=2)[C:17]=1[C:18]1[C:19]([CH3:29])=[C:20]2[C:25](=[C:26]([F:28])[CH:27]=1)[O:24][CH2:23][CH2:22][CH2:21]2)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:44])C=CC=CC=1.[CH3:54][Si:55]([CH3:60])([CH3:59])[CH2:56][CH2:57][OH:58].C([N:63]([CH2:66]C)CC)C>C1(C)C=CC=CC=1>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:36])=[N:14][C:15]2[N:16]([N:30]=[C:31]([NH:63][C:66]([O:58][CH2:57][CH2:56][Si:55]([CH3:60])([CH3:59])[CH3:54])=[O:44])[CH:32]=2)[C:17]=1[C:18]1[C:19]([CH3:29])=[C:20]2[C:25](=[C:26]([F:28])[CH:27]=1)[O:24][CH2:23][CH2:22][CH2:21]2)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:3])([CH3:4])[CH3:2]
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참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 180132-(Trimethylsilyl)ethanolHCID 199401P,P-Diphenylphosphinic azideHCID 712583786-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid

생성물 1

HCID 86695369
(2S)-ethyl 2-tert-butoxy-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-((2-(trimethylsilyl)ethoxy)carbonylamino)pyrazolo[1,5-a]pyrimidin-6-yl)acetate
수율 70.2%

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

A mixture of 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid (3.40 g, 5.79 mmol), diphenylphosphoryl azide (1.50 mL, 6.94 mmol), 2-(trimethylsilyl)ethanol (1.66 mL, 11.6 mmol), triethylamine (0.968 mL, 6.94 mmol) in toluene (100 mL) was refluxed for 16 h. It was then concentrated in vacuo. The residue was purified by biotage eluting with 20% EtOAc/hexane to isolate 2.5 g (70%) of (2S)-ethyl 2-tert-butoxy-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-((2-(trimethylsilyl)ethoxy)carbonylamino)pyrazolo[1,5-a]pyrimidin-6-yl)acetate as off-white solid. 1H NMR (500 MHz, CDCl3) δ 7.25 (s, 1H), 6.89 (s, 1H), 6.87 (d, J=6.9 Hz, 1H), 4.90 (s, 1H), 4.34 (m, 2H), 4.30 (m, 2H), 4.13 (d, J=7.1 Hz, 2H), 2.84-2.63 (m, 5H), 2.18 (m, 2H), 1.84 (s, 3H), 1.20 (t, J=7.1 Hz, 3H), 1.17 (s, 9H), 1.05 (m, 2H), 0.07 (s, 9H). LCMS (M+H)=615.4.

후처리

  1. temperaturewas refluxed for 16 h
  2. concentrationIt was then concentrated in vacuo
  3. customThe residue was purified by biotage
  4. washeluting with 20% EtOAc/hexane

출처 및 근거

ORD 기록
ord-6a6bbdbe4ccf487290101d27b1b67bce
출처 데이터셋
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09006235B2

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