Benzyl Bromide → (1R,2S)-2-(1-benzyl-3-iodo-1H-indazol-6-yl)-1'-methylspiro[cyclopropane-1,3'-indolin]-2'-one

HRID 1410364노트

반응식

HRID 1410364 반응식
[I:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([C@H:11]3[C@@:13]4([C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[N:15]([CH3:22])[C:14]4=[O:23])[CH2:12]3)=[CH:8][CH:9]=2)[NH:4][N:3]=1.[OH-].[K+].[CH:26]1[CH:31]=[CH:30][C:29]([CH2:32]Br)=[CH:28][CH:27]=1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[CH2:32]([N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[C:7]([C@H:11]3[C@@:13]4([C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[N:15]([CH3:22])[C:14]4=[O:23])[CH2:12]3)[CH:6]=2)[C:2]([I:1])=[N:3]1)[C:29]1[CH:30]=[CH:31][CH:26]=[CH:27][CH:28]=1

참가 물질

6

반응물 3

HCID 7498Benzyl BromideHCID 14797Potassium HydroxideHCID 178481340HCID 178481340, 화합물

생성물 1

HCID 86681514(1R,2S)-2-(1-benzyl-3-iodo-1H-indazol-6-yl)-1'-methylspiro[cyclopropane-1,3'-indolin]-2'-one

시약·촉매·용매 2

HCID 74236Tetrabutylammonium Bromide촉매HCID 6344Dichloromethane용매

실험 절차

A round-bottom flask was charged with (1R,2S)-2-(3-iodo-1H-indazol-6-yl)-1′-methylspiro[cyclopropane-1,3′-indolin]-2′-one (200 mg, 0.482 mmol), tetrabutylammonium bromide (2.0 mg, 0.005 mmol), CH2Cl2 (3.5 mL), and KOH (1.0 mL, 50% wt aqueous solution). The mixture was then treated with BnBr (69 uL, 0.578 mmol) and the reaction stirred for 18 h at which time the product was extracted with CH2Cl2 (3×) and the combined organic layers washed with brine and dried over MgSO4. After removal of solvent, purification using a Biotage Isolera (silica gel, 1-5% MeOH in DCM) gave the title compound. 1H NMR (400 MHz, CDCl3) δ 7.35 (d, 1H, J=8.2 Hz), 7.29-7.25 (m, 3H), 7.15-7.10 (m, 4H), 6.97 (d, 1H, J=8.3 Hz), 6.85 (d, 1H, J=8.0 Hz), 6.56 (t, 1H, J=7.3 Hz), 5.72 (d, J=7.5 Hz, 1H), 5.63-5.49 (m, 2H), 3.39 (t, J=8.8 Hz, 1H), 3.32 (s, 3H), 2.22-2.19 (m, 1H), 1.97-1.94 (m, 1H); MS ESI 506.1 [M+H]+, calcd for [C25H20IN3O+H]+ 506.07. Recrystallization from neat MeOH yielded clear, colorless crystals which were submitted for single crystal X-ray structure determination. The structure obtained (see FIGURE) confirmed the relative and absolute stereochemistry as (1R,2S), i.e. identical to that predicted by the “Sharpless mnemonic”. The crystallographic data is summarized in the table below.

후처리

  1. extractionwas extracted with CH2Cl2 (3×)
  2. washthe combined organic layers washed with brine
  3. dry with materialdried over MgSO4
  4. customAfter removal of solvent, purification

출처 및 근거

ORD 기록
ord-a6906e24e2904d2eb47f23b73d9f9f05
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921545B2

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