5-fluoro-2,3-dihydro-1H-isoindole hydrochloride → N-[4-(3-Piperidin-1-ylpropoxy)-benzoyl]-5-fluoroisoindoline hydrochloride

HRID 268730ノート

反応式

HRID 268730 の反応式
Cl.[F:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH2:8][NH:7][CH2:6]2.Cl.[N:13]1([CH2:19][CH2:20][CH2:21][O:22][C:23]2[CH:31]=[CH:30][C:26]([C:27]([Cl:29])=[O:28])=[CH:25][CH:24]=2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1>C(Cl)Cl>[ClH:29].[N:13]1([CH2:19][CH2:20][CH2:21][O:22][C:23]2[CH:24]=[CH:25][C:26]([C:27]([N:7]3[CH2:6][C:5]4[C:9](=[CH:10][CH:11]=[C:3]([F:2])[CH:4]=4)[CH2:8]3)=[O:28])=[CH:30][CH:31]=2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

参加物

4

反応物 2

HCID 179862865-fluoro-2,3-dihydro-1H-isoindole hydrochlorideHCID 218520624-(3-Piperidin-1-ylpropoxy)benzoyl chloride hydrochloride

生成物 1

HCID 17986281N-[4-(3-Piperidin-1-ylpropoxy)-benzoyl]-5-fluoroisoindoline hydrochloride収率 27.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A stirred mixture of 5-fluoroisoindoline hydrochloride (D8) (183 mg) and diethylaminoethylpolystyrene (626 mg, 3.2 mmol/g) in DCM (10 ml) at rt was treated with 4-(3-piperidin-1-ylpropoxy)-benzoyl chloride hydrochloride (223 mg) (D3). After 1 h the reaction mixture was chromatographed directly [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM)]. Fractions containing the required product were evaporated, redissolved in DCM, treated with excess hydrogen chloride (4M solution in dioxan) and then evaporated. The residue was triturated with acetone, filtered, washed with acetone and dried to yield the title compound (E11) (80 mg). MS electrospray (+ion) 383 (MH+). 1H NMR δ (DMSO-d6): 10.21 (1H, s), 7.61 (2H, d, J=8.8 Hz), 7.05-7.50 (3H, m), 7.01 (2H, d, J=8.8 Hz), 4.81 (4H, m), 4.13. (2H, t, J=6 Hz), 3.46 (2H, m), 3.15 (2H, m), 2.88 (2H, m), 2.21 (2H, m), 1.28-1.92 (6H, m).

後処理

  1. customAfter 1 h the reaction mixture was chromatographed directly [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM)]
  2. additionFractions containing the required product
  3. customwere evaporated
  4. dissolutionredissolved in DCM
  5. additiontreated with excess hydrogen chloride (4M solution in dioxan)
  6. customevaporated
  7. customThe residue was triturated with acetone
  8. filtrationfiltered
  9. washwashed with acetone
  10. customdried

出典と根拠

ORDレコード
ord-0f90194842b7439cafe6890eef33d238
出典データセット
uspto-grants-2008_11
特許番号
US07446103B2

反応ノート

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