1-Hydroxybenzotriazole → 1-Cyclobutyl-4-{[4-(1,1-dioxido-4-thiomorpholinyl)phenyl]carbonyl}hexahydro-1H-1,4-diazepine hydrochloride

HRID 2261236ノート

反応式

HRID 2261236 の反応式
[ClH:1].Cl.[CH:3]1([N:7]2[CH2:13][CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1.CCN(CC1C=CC=CC=1)CC.C=CC1C=CC=CC=1.C=CC1C=CC(C=C)=CC=1.C1C=CC2N(O)N=NC=2C=1.[O:54]=[S:55]1(=[O:70])[CH2:60][CH2:59][N:58]([C:61]2[CH:69]=[CH:68][C:64]([C:65](O)=[O:66])=[CH:63][CH:62]=2)[CH2:57][CH2:56]1>C(Cl)Cl.C(Cl)CCl>[ClH:1].[CH:3]1([N:7]2[CH2:13][CH2:12][CH2:11][N:10]([C:65]([C:64]3[CH:63]=[CH:62][C:61]([N:58]4[CH2:57][CH2:56][S:55](=[O:70])(=[O:54])[CH2:60][CH2:59]4)=[CH:69][CH:68]=3)=[O:66])[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1

参加物

7

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 27638174-(1,1-Dioxidothiomorpholino)benzoic acidHCID 16212021N-benzyl-N-ethylethanamine;1,4-bis(ethenyl)benzene;styreneHCID 574239521-Cyclobutyl-1,4-diazepane dihydrochloride

生成物 1

HCID 669300931-Cyclobutyl-4-{[4-(1,1-dioxido-4-thiomorpholinyl)phenyl]carbonyl}hexahydro-1H-1,4-diazepine hydrochloride収率 30.4%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 6344Dichloromethane溶媒

実験手順

1-(Cyclobutyl)-hexahydro-1H-1,4-diazepine dihydrochloride (D4) (0.15 g) was stirred with diethylaminomethyl polystyrene (1.0 g), HOBT (0.045 g), 4-(1,1-dioxido-4-thiomorpholinyl)benzoic acid (0.186 g) in DCM (5 ml). EDC (0.165 g) was then added and the reaction was stirred at rt for 16 h. The polymer supported base was filtered off and the filtrate was diluted with DCM (10 ml) and washed with saturated sodium hydrogen carbonate (2×15 ml). The organic layer was then loaded directly onto a silica column and eluted with 0-10% MeOH (containing 10% 0.880 ammonia solution)/DCM. The isolated free base product was dissolved in DCM (5 ml) and treated with excess 1N HCl/diethyl ether solution (1 ml) and stirred for 10 min. The mixture was evaporated (co-evaporated with acetone 2×10 ml), triturated with acetone, then dried at 50° C. under high vacuum for 16 h to yield the title compound (E9) as a pale solid (0.086 g). MS electrospray (+ion) 392 (MH+). 1H NMR δ (DMSO-d6): 10.5 (1H, s), 7.37 (2H, d, J=8.4 Hz), 7.07 (2H, d, J=8.8 Hz), 4.18-3.24 (10H, m), 3.11 (4H, m), 3.10-2.85 (2H, m), 2.45-1.98 (7H, m), 1.80-2.54 (2H, m).

後処理

  1. filtrationwas filtered off
  2. additionthe filtrate was diluted with DCM (10 ml)
  3. washwashed with saturated sodium hydrogen carbonate (2×15 ml)
  4. washeluted with 0-10% MeOH (containing 10% 0.880 ammonia solution)/DCM
  5. dissolutionThe isolated free base product was dissolved in DCM (5 ml)
  6. additiontreated with excess 1N HCl/diethyl ether solution (1 ml)
  7. stirringstirred for 10 min
  8. customThe mixture was evaporated (co-evaporated with acetone 2×10 ml)
  9. customtriturated with acetone
  10. customdried at 50° C. under high vacuum for 16 h

出典と根拠

ORDレコード
ord-e4d1d42da9e3447bb5d9b6e22d7b5fed
出典データセット
uspto-grants-2010_12
特許番号
US07846922B2

反応ノート

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