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Cesium carbonate → 4-(4-chloro-2-cyanophenyl)-N-(4-methoxybenzyl)-2-(methoxymethyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528648
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HRID 528648 반응식
[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][N:8]([C:25]2[S:26][CH:27]=[CH:28][N:29]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[NH:20][CH2:19][CH:18]([CH2:21][O:22][CH3:23])[O:17][C:16]=3[CH:24]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.[Cl:32][C:33]1[CH:34]=[CH:35][C:36](F)=[C:37]([CH:40]=1)[C:38]#[N:39].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O>[Cl:32][C:33]1[CH:34]=[CH:35][C:36]([N:20]2[CH2:19][CH:18]([CH2:21][O:22][CH3:23])[O:17][C:16]3[CH:24]=[C:12]([S:9]([N:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:31][CH:30]=4)[C:25]4[S:26][CH:27]=[CH:28][N:29]=4)(=[O:11])=[O:10])[CH:13]=[CH:14][C:15]2=3)=[C:37]([C:38]#[N:39])[CH:40]=1
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참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 936535-Chloro-2-fluorobenzonitrileHCID 89761839N-(4-methoxybenzyl)-2-(methoxymethyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

생성물 1

HCID 897619324-(4-chloro-2-cyanophenyl)-N-(4-methoxybenzyl)-2-(methoxymethyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide수율 87.9%

시약·촉매·용매 2

HCID 962
Water
용매
HCID 6228Dimethylformamide용매

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온도
80 °C

실험 절차

To a solution of N-(4-methoxybenzyl)-2-(methoxymethyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (150 mg, 0.324 mmol) and 5-chloro-2-fluorobenzonitrile (50.55 mg, 0.324 mmol, Aldrich) in DMF (5.0 mL) was added Cs2CO3 (210 mg, 7.95 mmol) and the reaction mixture was heated at 80° C. for 16 h. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude material which was purified by column chromatography (silica gel 100-200 mesh and 0-30% ethyl acetate in hexane) to obtain 4-(4-chloro-2-cyanophenyl)-N-(4-methoxybenzyl)-2-(methoxymethyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (170 mg, 87.6%) as an off white solid. m/z (ESI) 596.8 (M+H)+.

후처리

  1. extractionextracted with ethyl acetate (2×50 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto obtain the crude material which
  6. customwas purified by column chromatography (silica gel 100-200 mesh and 0-30% ethyl acetate in hexane)

출처 및 근거

ORD 기록
ord-55051fc73f1140019de144b22dc24e4e
출처 데이터셋
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09346798B2

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