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

HRID 2181444ノート

反応式

HRID 2181444 の反応式
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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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

後処理

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

出典と根拠

ORDレコード
ord-e68d0246364748f495f15bc38583d90f
出典データセット
uspto-grants-2005_05
特許番号
US06891066B2

反応ノート

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