Hydrochloric Acid → (+/-)-1-(3-Amino-4-cyano-benzyl)-4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-6-oxo-piperazine-2-carboxylic acid methyl ester

HRID 1432943노트

반응식

HRID 1432943 반응식
[CH3:1][O:2][C:3]([CH:5]1[CH2:10][N:9]([S:11]([C:14]2[S:18][C:17]3[CH:19]=[C:20]([Cl:23])[CH:21]=[CH:22][C:16]=3[CH:15]=2)(=[O:13])=[O:12])[CH2:8][C:7](=[O:24])[N:6]1[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[C:28]([N:34]=C(C2C=CC=CC=2)C2C=CC=CC=2)[CH:27]=1)=[O:4].C1COCC1.Cl>Cl.CO>[CH3:1][O:2][C:3]([CH:5]1[CH2:10][N:9]([S:11]([C:14]2[S:18][C:17]3[CH:19]=[C:20]([Cl:23])[CH:21]=[CH:22][C:16]=3[CH:15]=2)(=[O:12])=[O:13])[CH2:8][C:7](=[O:24])[N:6]1[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[C:28]([NH2:34])[CH:27]=1)=[O:4]

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 54128933(+/-)-1-[3-(Benzhydrylidene-amino)-4-cyano-benzyl]-4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-6-oxo-piperazine-2-carboxylic acid methyl ester

생성물 1

HCID 54383939(+/-)-1-(3-Amino-4-cyano-benzyl)-4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-6-oxo-piperazine-2-carboxylic acid methyl ester수율 101.2%

시약·촉매·용매 2

HCID 313Hydrochloric Acid촉매HCID 887Methanol용매

실험 절차

Concentrated HCl (12M, one drop) is added at 0° C. to a mixture containing (±)-1-[3-(benzhydrylidene-amino)-4-cyano-benzyl]-4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-6-oxo-piperazine-2-carboxylic acid methyl ester (60 mg, 0.08 mmol) in MeOH (5 mL). Added THF (2 mL) followed by a second drop of 12M HCl and warmed reaction mixture to ambient temperature. The reaction is quenched by pouring the reaction mixture onto a 1:1 mixture of CH2Cl2/aqueous NaHCO3 and the layers are separated. The aqueous phase is washed with CH2Cl2 and then the combined organic phase is washed with brine, dried over anhydrous MgSO4, filtered and concentrated. The crude residue is chromatographed on silica gel (CH2Cl2 to 4% MeOH/CH2Cl2) to provide 42 mg (93%) of the title compound. 1H NMR (300 MHz, CDCl3) δ2.98 (dd, J=12.5, 3.5 Hz, 1H), 3.60 (d, J=16.8 Hz, 1H), 3.69 (d, J=15.3 Hz, 1H), 3.79 (s, 3H), 3.98 (m, 1H), 4.21-4.31 (m, 2H), 4.44 (br s, 2H), 5.36 (d, J=15.3 Hz, 1H), 6.47 (dd, J=8.0, 1.4 Hz, 1H), 6.54 (s, 1H), 7.26 (d, J=8.0 Hz, 1H), 7.45 (dd, J=8.5, 1.8 Hz, 1H), 7.80-7.86 (m, 3H) ppm; MS (ISP loop): m/z 519 (M+H).

후처리

  1. temperaturewarmed
  2. customreaction mixture to ambient temperature
  3. customThe reaction is quenched
  4. additionby pouring the reaction mixture
  5. additiononto a 1:1 mixture of CH2Cl2/aqueous NaHCO3
  6. customthe layers are separated
  7. washThe aqueous phase is washed with CH2Cl2
  8. washthe combined organic phase is washed with brine
  9. dry with materialdried over anhydrous MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude residue is chromatographed on silica gel (CH2Cl2 to 4% MeOH/CH2Cl2)

출처 및 근거

ORD 기록
ord-11d8ead035764227862f0ba3e950ad5d
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07612075B2

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