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Allyl Alcohol → (2S)-Methyl 2-(7-(4-allylchroman-6-yl)-2-(2'-(allyloxy)-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 1400716
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인쇄 미리보기

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HRID 1400716 반응식
[CH2:1]([CH:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[N:19]4[N:20]=[C:21]([C:23]5[CH:24]=[C:25]([C:29]6[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=6[OH:35])[CH:26]=[CH:27][CH:28]=5)[CH:22]=[C:18]4[N:17]=[C:16]([CH3:36])[C:15]=3[C@H:37]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[C:38]([O:40][CH3:41])=[O:39])[CH:12]=2)[O:7][CH2:6][CH2:5]1)[CH:2]=[CH2:3].[CH2:47](O)[CH:48]=[CH2:49].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[CH2:1]([CH:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[N:19]4[N:20]=[C:21]([C:23]5[CH:24]=[C:25]([C:29]6[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=6[O:35][CH2:49][CH:48]=[CH2:47])[CH:26]=[CH:27][CH:28]=5)[CH:22]=[C:18]4[N:17]=[C:16]([CH3:36])[C:15]=3[C@H:37]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[C:38]([O:40][CH3:41])=[O:39])[CH:12]=2)[O:7][CH2:6][CH2:5]1)[CH:2]=[CH2:3]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 4

HCID 7858Allyl AlcoholHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 86710768HCID 86710768, 화합물

생성물 1

HCID 89971576(2S)-Methyl 2-(7-(4-allylchroman-6-yl)-2-(2'-(allyloxy)-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate수율 105.8%

시약·촉매·용매

1
HCID 8028Tetrahydrofuran용매

실험 절차

A solution of (2S)-methyl 2-(7-(4-allylchroman-6-yl)-2-(2′-hydroxy-[1,1′-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.350 g, 0.567 mmol) in dry THF (12 ml) was treated sequentially with allyl alcohol (0.116 ml, 1.700 mmol), Ph3P (0.446 g, 1.700 mmol) and DEAD (0.269 ml, 1.700 mmol), and the reaction was stirred for 2 h. The reaction was concentrated, and the residue was purified by biotage (24 g SiO2, 0% (3 CV), 0-60% (15 CV), 60% (2 CV), EtOAc in hexane). The residue after concentration was taken up in Et2O (20 mL) and washed with water (2×20 mL) to remove residual allyl alcohol, then dried (MgSO4), filtered, and concentrated, affording the desired product (0.4 g, 0.6 mmol, quant.) as a viscous clear oil. 1H NMR (500 MHz, CDCl3) δ 8.11-8.04 (m, 1H), 7.90-7.84 (m, 1H), 7.58-7.36 (m, 5H), 7.35-7.29 (m, 1H), 7.06 (t, J=7.4 Hz, 1H), 7.02-6.93 (m, 2H), 6.90 (s, 1H), 6.04-5.91 (m, 1H), 5.90-5.78 (m, 1H), 5.37-5.30 (m, 4H), 5.27-5.13 (m, 4H), 5.12-5.02 (m, 2H), 4.55 (d, J=4.9 Hz, 2H), 4.30 (br. s., 2H), 3.82 (s, 3H), 2.68-2.63 (m, 3H), 1.01-0.93 (m, 9H). LCMS (M+H)=658.6.

후처리

  1. concentrationThe reaction was concentrated
  2. customthe residue was purified by biotage (24 g SiO2, 0% (3 CV), 0-60% (15 CV), 60% (2 CV), EtOAc in hexane)
  3. concentrationThe residue after concentration
  4. washwashed with water (2×20 mL)
  5. customto remove residual allyl alcohol
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-645f8df0852e4eecbdcd721e0e80999d
출처 데이터셋
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08906929B2

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