Trifluoroacetic acid → 3-{[(1-oxidoquinolin-4-yl)methyl]amino}-N-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide

HRID 497164노트

반응식

HRID 497164 반응식
[N+:1]1([O-:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH:11]=O)=[CH:3][CH:2]=1.[NH2:14][C:15]1[CH:19]=[CH:18][S:17][C:16]=1[C:20]([NH:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=1)=[O:21].FC(F)(F)C(O)=O.C([SiH](CC)CC)C.[OH-].[Na+]>O.ClCCl>[O-:13][N+:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH2:11][NH:14][C:15]2[CH:19]=[CH:18][S:17][C:16]=2[C:20]([NH:22][C:23]2[CH:24]=[CH:25][C:26]([O:29][C:30]([F:33])([F:31])[F:32])=[CH:27][CH:28]=2)=[O:21])=[CH:3][CH:2]=1

참가 물질

8

반응물 5

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 14798Sodium HydroxideHCID 11229066Quinoline-4-carbaldehyde 1-oxideHCID 219638853-amino-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide

생성물 1

HCID 103894733-{[(1-oxidoquinolin-4-yl)methyl]amino}-N-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

A solution of quinoline-4-carboxaldehyde 1-oxide (0.12 g, 0.69 mmol), 3-amino-N-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide (0.21 g, 0.69 mmol), dichloromethane (2 ml) and trifluoroacetic acid (2 ml) was heated at 50° C. for 2 hr, then cooled to room temperature, treated with triethylsilane (0.22 ml, 1.38 mmol) and stirred at 50° C. for another 2 h. After this time the mixture was diluted with water (40 ml), basified (pH 9) with 2M NaOH (aq) and extracted with ethyl acetate (3×20 ml). The extracts were washed with water (30 ml) and brine (30 ml), then dried (MgSO4) and concentrated in vacuo to give crude product. This material was chromatographed over silica gel eluting with 15% acetonitrile/CH2Cl2, and the isolated product further purified by crystallization from acetonitrile to give 3-{[(1-oxidoquinolin-4-yl)methyl]amino}-N-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide. MS (ES+): 460 [MH+]. 1H NMR (DMSO-d6, 400 MHz): δ 5.00 (s, 2H), 6.87 (d, J=5.6 Hz, 1H), 7.25-7.40 (m, 3H), 7.65 (d, J=5.3 Hz, 1H), 7.73-7.91 (m, 4H), 8.0 (t, J=6.4 Hz, 1H), 8.30 (d, J=7.1 Hz, 1H), 8.56 (d, J=6.3 Hz, 1H), 8.61 (d, J=8.3 Hz, 1H), 9.60 (s, 1H).

후처리

  1. extractionextracted with ethyl acetate (3×20 ml)
  2. washThe extracts were washed with water (30 ml) and brine (30 ml)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customto give crude product
  6. customThis material was chromatographed over silica gel eluting with 15% acetonitrile/CH2Cl2
  7. customthe isolated product further purified by crystallization from acetonitrile

출처 및 근거

ORD 기록
ord-f37c73ad8bf445e081a6d8cda33d4781
출처 데이터셋
uspto-grants-2005_09
특허 번호
US06949563B2

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