Diisopropylethylamine → N-[4-(3-chloropropoxy)-naphthalen-1-yl]-3-fluoro-5-piperidin-1-yl-benzamide

HRID 1641258

反応式

HRID 1641258 の反応式
[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([NH2:16])=[CH:8][CH:7]=1.[F:17][C:18]1[CH:19]=[C:20]([CH:24]=[C:25]([N:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[CH:26]=1)[C:21](O)=[O:22].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([NH:16][C:21](=[O:22])[C:20]2[CH:24]=[C:25]([N:27]3[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]3)[CH:26]=[C:18]([F:17])[CH:19]=2)=[CH:8][CH:7]=1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595531174-(3-Chloropropoxy)naphthalen-1-amineHCID 595531803-Fluoro-5-piperidinylbenzoic acid

生成物 1

HCID 59553319N-[4-(3-chloropropoxy)-naphthalen-1-yl]-3-fluoro-5-piperidin-1-yl-benzamide収率 65%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 4-(3-chloropropoxy)naphthalen-1-amine (2.85 g, 10.5 mmol) and 3-fluoro-5-piperidin-1-ylbenzoic acid (3.52 g, 15.7 mmol), in DMF (30 ml) is added HBTU (7.1 g, 18.9 mmol), and Hunig's base (6.0 ml, 33.6 mmol). The mixture is stirred overnight at room temperature then diluted with ethyl acetate (200 ml) and washed with water (3×100 ml). The organic layer is dried over Na2SO4 and evaporated. The residue is purified by column chromatography on silica gel to yield N-[4-(3-chloropropoxy)-naphthalen-1-yl]-3-fluoro-5-piperidin-1-yl-benzamide as a white solid (3.0 g, 65%). Mp: 181-182° C. 1H NMR (300 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.26 (m, 1H), 7.87 (m, 1H), 7.55 (m, 2H), 7.46 (s, 1H), 7.43 (d, J=8.1 Hz, 1H), 7.17 (d, J=9.3 Hz, 1H), 7.04 (d, J=8.4 Hz, 1H), 6.97 (d, J=10.5 Hz, 1H), 4.33 (t, J=6.0 Hz, 2H), 3.96(t, J=6.6, Hz, 2H), 3.29 (m, 4H), 2.34 (m, 6H), 1.59 (m, 6H). MS: 441.3 (M+1).

後処理

  1. washwashed with water (3×100 ml)
  2. dry with materialThe organic layer is dried over Na2SO4
  3. customevaporated
  4. customThe residue is purified by column chromatography on silica gel

出典と根拠

ORDレコード
ord-f2e0b134ed4b4004b4310445b8e9cfda
出典データセット
uspto-grants-2012_02
特許番号
US08114873B2

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