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

HRID 268730노트

반응식

HRID 268730 반응식
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

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-0f90194842b7439cafe6890eef33d238
출처 데이터셋
uspto-grants-2008_11
특허 번호
US07446103B2

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