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Sodium hydride → (S)-Ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methyl-2-(((5-methyl-2-((S)-pent-4-en-2-yloxy)benzyl)oxy)methyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 921137
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HRID 921137 반응식
[CH2:1]([O:4][C:5]1([CH3:34])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20]I)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:22])[C:12]=2[C@H:23]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[CH3:35][C:36]1[CH:37]=[CH:38][C:39]([O:44][C@H:45]([CH2:47][CH:48]=[CH2:49])[CH3:46])=[C:40]([CH2:42][OH:43])[CH:41]=1.[H-].[Na+]>CN(C=O)C>[CH2:1]([O:4][C:5]1([CH3:34])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20][O:43][CH2:42][C:40]4[CH:41]=[C:36]([CH3:35])[CH:37]=[CH:38][C:39]=4[O:44][C@H:45]([CH2:47][CH:48]=[CH2:49])[CH3:46])[CH:19]=[C:15]3[N:14]=[C:13]([CH3:22])[C:12]=2[C@H:23]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:7][CH2:6]1)[CH:2]=[CH2:3]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 118307102(S)-(5-methyl-2-(pent-4-en-2-yloxy)phenyl)methanolHCID 118318796(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(iodomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

생성물 1

HCID 131734906(S)-Ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methyl-2-(((5-methyl-2-((S)-pent-4-en-2-yloxy)benzyl)oxy)methyl)pyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate
수율 22.3%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

(S)-Ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(iodomethyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.45 g, 0.770 mmol) was dissolved in 1 mL DMF to this was added (S)-(5-methyl-2-(pent-4-en-2-yloxy)phenyl)methanol (0.191 g, 0.924 mmol) as a solution in 1 mL DMF. NaH-60% wt/wt in oil (47 mg, 1.16 mmol) was added and the reaction mixture was stirred for 5 hours. The reaction was quenched with 1N HCl then transferred to a separatory funnel where the product was extracted with ethyl acetate. The organic solution was dried over Na2SO4. After filtration the solvent was removed under vacuum and the product purified by silica gel chromatography using a Biotage apparatus to isolate the title compound as an oil (114 mg). 1H NMR (400 MHz, CDCl3) δ 1.21-1.24 (15H, overlapping s and m), 1.32 (3H, d), 1.65-1.8 (4H, br m), 2.35 (3H, s), 2.50 (2H, m), 2.61 (3H, s), 3.0-3.5 (4H, very broad m), 3.75 (2H, s), 4.21 (2H, m), 4.45 (1H, m), 4.66 (2H, br s), 4.77 (2H, s), 5.06-5.22 (4H, overlapping m), 5.32 (1H, s), 5.85-6.2 (2H, overlapping m), 6.59 (1H, s), 6.71 (1H, s), 6.77 (1H, d), 7.34 (1H, d).

후처리

  1. customThe reaction was quenched with 1N HCl
  2. customthen transferred to a separatory funnel
  3. extractionwhere the product was extracted with ethyl acetate
  4. dry with materialThe organic solution was dried over Na2SO4
  5. filtrationAfter filtration the solvent
  6. customwas removed under vacuum
  7. customthe product purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-9dff74479d8d4300952c5d39b1994a49
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09273067B2

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