2,3,4-Trifluorobenzoic acid → 3,4-difluoro-2-{2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilino}benzoic acid

HRID 2181444노트

반응식

HRID 2181444 반응식
F[C:2]1[C:10]([F:11])=[C:9]([F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[F:13][C:14]1[CH:20]=[C:19]([C:21]#[C:22][CH2:23][O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[CH:18]=[CH:17][C:15]=1[NH2:16].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[F:11][C:10]1[C:2]([NH:16][C:15]2[CH:17]=[CH:18][C:19]([C:21]#[C:22][CH2:23][O:24][CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][O:26]3)=[CH:20][C:14]=2[F:13])=[C:3]([CH:7]=[CH:8][C:9]=1[F:12])[C:4]([OH:6])=[O:5]

참가 물질

5

반응물 3

HCID 3029322,3,4-Trifluorobenzoic acidHCID 2733832Lithium HexamethyldisilazideHCID 220256372-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]aniline

생성물 1

HCID 220256553,4-difluoro-2-{2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilino}benzoic acid

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

2,3,4-Trifluorobenzoic acid and 2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]aniline were reacted in the presence of LiHMDS solution in THF by the general procedure of Example 1, Step B. After workup, followed by purification by chromatography on silica gel (50% EtOAc/PE as eluant), 3,4-difluoro-2-{2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilino}benzoic acid was isolated as a cream-yellow solid (68%); m.p. (Et2O/hexane) 164-166° C. 1H NMR [400 MHz, (CD3)2SO] δ 13.60 (v br s, 1 H), 9.27 (br s, 1 H), 7.83 (ddd, J=8.2, 6.1, 1.9 Hz, 1 H), 7.36 (dd, J=12.0, 1.7 Hz, 1 H), 7.21-7.11 (m, 2 H), 6.96 (td, J=8.8, 5.5 Hz, 1 H), 4.80 (br s, 1 H), 4.47 (d, J=16.0 Hz, 1 H), 4.38 (d, J=16.0 Hz, 1 H), 3.79-3.71 (m, 2 H), 3.51-3.45 (m, 2 H), 1.77-1.61 (m, 2 H), 1.56-1.44 (m, 4 H). Anal. calcd. for C21H18F3NO4: C, 62.2; H, 4.5; N, 3.5. Found C, 62.5; H, 4.4; N, 3.6. Step C: Preparation of 3,4-difluoro-2-{2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilino}-N-(2-hydroxyethoxy)benzamide

후처리

  1. customAfter workup, followed by purification by chromatography on silica gel (50% EtOAc/PE as eluant)

출처 및 근거

ORD 기록
ord-e68d0246364748f495f15bc38583d90f
출처 데이터셋
uspto-grants-2005_05
특허 번호
US06891066B2

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