N-benzyl-N-ethylethanamine;1,4-bis(ethenyl)benzene;styrene → N-{2-Chloro-4-[(1-cyclobutyl-4-piperidinyl)oxy]benzoyl}-5-fluoro-isoindoline hydrochloride

HRID 268744ノート

反応式

HRID 268744 の反応式
Cl.[Cl:2][C:3]1[CH:11]=[C:10]([O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH:19]3[CH2:22][CH2:21][CH2:20]3)[CH2:15][CH2:14]2)[CH:9]=[CH:8][C:4]=1[C:5](Cl)=[O:6].CCN(CC1C=CC=CC=1)CC.C=CC1C=CC=CC=1.C=CC1C=CC(C=C)=CC=1.Cl.[F:54][C:55]1[CH:56]=[C:57]2[C:61](=[CH:62][CH:63]=1)[CH2:60][NH:59][CH2:58]2>C(Cl)Cl>[ClH:2].[Cl:2][C:3]1[CH:11]=[C:10]([O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH:19]3[CH2:22][CH2:21][CH2:20]3)[CH2:15][CH2:14]2)[CH:9]=[CH:8][C:4]=1[C:5]([N:59]1[CH2:58][C:57]2[C:61](=[CH:62][CH:63]=[C:55]([F:54])[CH:56]=2)[CH2:60]1)=[O:6]

参加物

5

反応物 3

HCID 16212021N-benzyl-N-ethylethanamine;1,4-bis(ethenyl)benzene;styreneHCID 179862522-Chloro-4-[(1-cyclobutyl-4-piperidinyl)oxy]benzoyl chloride hydrochlorideHCID 179862865-fluoro-2,3-dihydro-1H-isoindole hydrochloride

生成物 1

HCID 17986248N-{2-Chloro-4-[(1-cyclobutyl-4-piperidinyl)oxy]benzoyl}-5-fluoro-isoindoline hydrochloride収率 109.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A stirred mixture of 2-chloro-4-[(1-cyclobutyl-4-piperidinyl)oxy]benzoyl chloride hydrochloride (D36) (0.20 g) and diethylaminomethyl polystyrene (3.2 mmol/g, 0.8 g) in DCM (10 ml) at rt was treated with 5-fluoroisoindoline hydrochloride (D8) (0.10 g) and stirred for 16 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 (1M solution in diethyl ether) and then concentrated. The residue was crystallised from acetone to yield the title compound (E65) as a white solid (0.14 g). MS electrospray (+ion) 430/432 (MH+). 1H NMR δ (DMSO-d6): 10.48 (1H, s), 7.46-7.06 (6H, m), 4.88-4.60 (3H, m), 4.51 (2H, m), 3.80-3.55 (1H, m), 3.46-3.18 (2H, m), 2.88 (2H, m), 2.38-1.64 (10H, m).

後処理

  1. customThe 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 (1M solution in diethyl ether)
  6. concentrationconcentrated
  7. customThe residue was crystallised from acetone

出典と根拠

ORDレコード
ord-22a46e2b3ac24108851f9a5422b5e2a0
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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