Diisopropylethylamine → N-(2-acetamidopyrimidin-5-yl)-6-chloro-3-(3-(trifluoromethyl)phenylamino)benzo[d]isoxazole-7-carboxamide

HRID 253700노트

반응식

HRID 253700 반응식
[Cl:1][C:2]1[CH:21]=[CH:20][C:5]2[C:6]([NH:9][C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=3)=[N:7][O:8][C:4]=2[C:3]=1[C:22]([OH:24])=O.CCN(C(C)C)C(C)C.[NH2:34][C:35]1[CH:36]=[N:37][C:38]([NH:41][C:42](=[O:44])[CH3:43])=[N:39][CH:40]=1>CN(C=O)C>[C:42]([NH:41][C:38]1[N:39]=[CH:40][C:35]([NH:34][C:22]([C:3]2[C:4]3[O:8][N:7]=[C:6]([NH:9][C:10]4[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:17])([F:19])[F:18])[CH:11]=4)[C:5]=3[CH:20]=[CH:21][C:2]=2[Cl:1])=[O:24])=[CH:36][N:37]=1)(=[O:44])[CH3:43]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 20387481N-(5-aminopyrimidin-2-yl)acetamideHCID 441404356-Chloro-3-(3-(trifluoromethyl)phenylamino)benzo[d]isoxazole-7-carboxylic acid

생성물 1

HCID 25068624N-(2-acetamidopyrimidin-5-yl)-6-chloro-3-(3-(trifluoromethyl)phenylamino)benzo[d]isoxazole-7-carboxamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

A round-bottomed flask was charged with 6-chloro-3-(3-(trifluoromethyl)phenylamino)benzo[d]isoxazole-7-carboxylic acid (0.1 g, 0.28 mmol, made by the method described in Example 1), n,n-diisopropylethylamine (0.07 mL, 0.42 mmol), o-(7-azabenzotriazol-1-yl)-n,n,n′,n-tetramethyluronium hexafluorophosphate (0.15 g, 0.39 mmol), and DMF (1 mL). This mixture was stirred for 15 min before N-(5-aminopyrimidin-2-yl)acetamide (0.045 g, 0.29 mmol, Step B) was introduced. The reaction mixture was stirred at 60° C. for 16 h, then partitioned between EtOAc (15 ml) and brine (10 mL). The aqueous layer was back exacted with EtOAc (3×10 mL) and the combined EtOAc layer was dried (Na2SO4) and concentrated. The crude product was dissolved in DCM and chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 0% to 4% of MeOH in CH2Cl2, to provide N-(2-acetamidopyrimidin-5-yl)-6-chloro-3-(3-(trifluoromethyl)phenylamino)benzo[d]isoxazole-7-carboxamide as an off-white solid. MS (ESI, pos. ion) m/z: 491 (M+1).

후처리

  1. additionwas introduced
  2. custompartitioned between EtOAc (15 ml) and brine (10 mL)
  3. dry with materialthe combined EtOAc layer was dried (Na2SO4)
  4. concentrationconcentrated
  5. dissolutionThe crude product was dissolved in DCM
  6. customchromatographed through a Redi-Sep® pre-packed silica gel column (40 g)
  7. washeluting with a gradient of 0% to 4% of MeOH in CH2Cl2

출처 및 근거

ORD 기록
ord-16e893917d754908970c2836eb90c14b
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07872128B2

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