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Dimethylformamide → (4-{3-[(2,3-difluoro-phenyl)-acetyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-cyclohex-3-enyl)-carbamic acid tert-butyl ester

HRID 269505
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HRID 269505 반응식
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1C=N[O:12][C:13]=1[C:14]1[C:22]2[C:17](=[N:18][CH:19]=[C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:21]=2)[NH:16][CH:15]=1.C[N:30]([CH:32]=[O:33])C.[C:34]([O-])([O-])=O.[Na+].[Na+].ClC1C(Cl)=CC=CC=1[C:48]1C=N[O:51][C:52]=1[C:53]1C2C(=NC=CC=2)NC=1>CS(C)=O>[C:52]([O:51][C:32](=[O:33])[NH:30][CH:26]1[CH2:25][CH2:24][C:23]([C:20]2[CH:21]=[C:22]3[C:14]([C:13](=[O:12])[CH2:9][C:3]4[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=4[F:1])=[CH:15][NH:16][C:17]3=[N:18][CH:19]=2)=[CH:28][CH2:27]1)([CH3:53])([CH3:34])[CH3:48]
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HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 1354836473-[4-(2,3-Dichloro-phenyl)-isoxazol-5-yl]-1H-pyrrolo[2, 3-b]pyridineHCID 1360665193-[4-(2,3-Difluoro-phenyl)-isoxazol-5-yl]-5-phenyl-1H-pyrrolo[2,3-b]pyridine

생성물 1

HCID 59832239(4-{3-[(2,3-difluoro-phenyl)-acetyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-cyclohex-3-enyl)-carbamic acid tert-butyl ester
수율 56%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

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온도
80 °C

실험 절차

To a solution of the above boronic ester (1.0 g, 2.5 mmol), trifluoro-methanesulfonic acid 4-tert-butoxycarbonylamino-cyclohex-1-enyl ester (690 mg, 2.0 mmol, prepared from (4-Oxo-cyclohexyl)-carbamic acid tert-butyl ester (Heterocycles 58 (2002) 471-504)) in a mixed solvent of DMF (15 ml) and DMSO (6 ml) was added aqueous 2.0M Na2CO3 (2 ml, 4 mmol) and PdCl2(PPh3) 2 The mixture was degassed and heated at 80° C. under Argon for 72 h, and then concentrated under high vacuum to remove DMF. The residue was suspended in aqueous NaHCO3, then filtered. The solid was purified for FC to give (4-{3-[(2,3-difluoro-phenyl)-acetyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-cyclohex-3-enyl)-carbamic acid tert-butyl ester as a white solid (530 mg) in 56% yield, LC-MS: m/e=468.4 (M+H), 466.4 (M−H). 1H-NMR (500 MHz, CDCl3) 13.41 (br.s, 1H), 9.23 (s, 1H), 8.44 (s, 1H), 8.38 (s, 1H), 7.09 (m, 3H), 6.24 (s, 1H), 4.56 (br. s, 1H), 4.32 (s, 2H), 3.90 (br.s, 1H), 2.63 (m, 3H), 2.13 (m, 2H), 1.28 (m, 1H), 1.49 (s, 9H).

후처리

  1. customwas degassed
  2. concentrationconcentrated under high vacuum
  3. customto remove DMF
  4. filtrationfiltered
  5. customThe solid was purified for FC

출처 및 근거

ORD 기록
ord-0176be0e41604a36ad25c6ce128846c9
출처 데이터셋
uspto-grants-2008_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07446199B2

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