Diisopropylethylamine → N-{3-[(4s,6s)-2-Amino-4-(Fluoromethyl)-6-(Trifluoromethyl)-5,6-Dihydro-4h-1,3-Oxazin-4-Yl]-4-Fluorophenyl}-5-Cyanopyridine-2-Carboxamide

HRID 930298노트

반응식

HRID 930298 반응식
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:21])=[C:6]([C@:8]2([CH2:19][F:20])[CH2:13][C@@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C:10]([NH2:18])=[N:9]2)[CH:7]=1.C(N(CC)C(C)C)(C)C.[C:31]([C:33]1[CH:34]=[CH:35][C:36]([C:39](O)=[O:40])=[N:37][CH:38]=1)#[N:32].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>C(Cl)Cl.O>[NH2:18][C:10]1[O:11][C@H:12]([C:14]([F:17])([F:15])[F:16])[CH2:13][C@:8]([C:6]2[CH:7]=[C:2]([NH:1][C:39](=[O:40])[C:36]3[CH:35]=[CH:34][C:33]([C:31]#[N:32])=[CH:38][N:37]=3)[CH:3]=[CH:4][C:5]=2[F:21])([CH2:19][F:20])[N:9]=1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 124007345-Cyanopyridine-2-carboxylic acidHCID 86732112(4S,6S)-4-(5-amino-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine

생성물 1

HCID 71305057N-{3-[(4s,6s)-2-Amino-4-(Fluoromethyl)-6-(Trifluoromethyl)-5,6-Dihydro-4h-1,3-Oxazin-4-Yl]-4-Fluorophenyl}-5-Cyanopyridine-2-Carboxamide수율 42%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (4S,6S)-4-(5-amino-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (2a, 0.125 g, 0.404 mmol) in DCM (3 mL) was added N,N-diisopropylethylamine (0.074 mL, 0.424 mmol, Aldrich), 5-cyanopicolinic acid (0.060 g, 0.404 mmol, Aldrich) and 1-propanephosphonic acid cyclic anhydride (50% solution in ethyl acetate; 0.238 mL, 0.404 mmol, Alfa Aesar). The reaction was stirred at ambient temperature for 15 minutes. The reaction was diluted with water and DCM. The organic layer was separated and washed sequentially with aqueous saturated sodium bicarbonate solution and brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The crude material was purified by silica gel flash chromatography (gradient of 10-70% EtOAc in hexanes) to afford the title compound as a white solid. (0.0745 g, 0.170 mmol, 42.0% yield). MS m/z=440.0 [M+H]+. Calculated for C19H14F5N5O2: 439.34

후처리

  1. customThe organic layer was separated
  2. washwashed sequentially with aqueous saturated sodium bicarbonate solution and brine
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material was purified by silica gel flash chromatography (gradient of 10-70% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-07fccdd553ea4d0f8345ae9910f3fcd0
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09296734B2

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