Trifluoroacetic acid → 4-(4-Chloro-2-methoxyphenyl)-1-(9-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridin-2(1H)-one hydrochloride

HRID 930764노트

반응식

HRID 930764 반응식
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:27][CH2:26][C:25]2[C:24]3[C:19](=[CH:20][C:21]([N:28]4[CH:33]=[CH:32][C:31]([C:34]5[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][C:35]=5[O:41][CH3:42])=[CH:30][C:29]4=[O:43])=[CH:22][CH:23]=3)[N:18]([CH3:44])[C:17]=2[CH2:16]1)=O)CCC>C(Cl)Cl>[ClH:40].[Cl:40][C:37]1[CH:38]=[CH:39][C:34]([C:31]2[CH:32]=[CH:33][N:28]([C:21]3[CH:20]=[C:19]4[C:24]([C:25]5[CH2:26][CH2:27][NH:15][CH2:16][C:17]=5[N:18]4[CH3:44])=[CH:23][CH:22]=3)[C:29](=[O:43])[CH:30]=2)=[C:35]([O:41][CH3:42])[CH:36]=1

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 86727940butyl-7-(4-(4-chloro-2-methoxyphenyl)-2-oxopyridin-1(2H)-yl)-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate

생성물 1

HCID 686568294-(4-Chloro-2-methoxyphenyl)-1-(9-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridin-2(1H)-one hydrochloride

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Trifluoroacetic acid (1.0 mL) was added to a solution of ten-butyl-7-(4-(4-chloro-2-methoxyphenyl)-2-oxopyridin-1(2H)-yl)-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (0.23 g, 0.44 mmol) in CH2Cl2 (2 mL) under argon and stirred for 1 h. The mixture was concentrated under reduced pressure, and the residue was partitioned between CH2Cl2 and saturated NaHCO3 solution. The organic phase was removed, and the aqueous phase was extracted with CH2Cl2 (10×25 mL). The combined organic extracts were washed with brine (25 mL), dried over Na2SO4, and concentrated under reduced pressure. Flash column chromatography (12 g ISCO CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 2 column volumes to 0:100 over 20 column volumes and hold for 10 column volumes) provided the free base of the title compound. The free base was converted to the HCl salt using 2 N HCl in Et2O as of Example 129 (step b), providing the title compound (0.13 g, 33%) as a yellow solid: mp 294-300° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.43 (br s, 2H), 7.65 (d, J=7.0 Hz, 1H), 7.61 (d, J=1.5 Hz, 1H), 7.59 (d, J=8.0 Hz, 1H), 7.44 (d, J=8.5 Hz, 1H), 7.26 (d, J=2.0 Hz, 1H), 7.13 (dd, J=8.5, 2.0 Hz, 1H), 7.09 (dd, J=8.0, 2.0 Hz, 1H), 6.56 (d, J=2.0 Hz, 1H), 6.47 (dd, J=7.0, 1.5 Hz, 1H), 4.49-4.47 (m, 2H), 3.87 (m, 3H), 3.69 (s, 3H), 3.47-3.43 (m, 2H), 3.00-2.97 (m, 2H); ESI MS m/z 420 [M+H]+; HPLC (Method A) 96.7% (AUC), tR=15.5 min.

후처리

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customthe residue was partitioned between CH2Cl2 and saturated NaHCO3 solution
  3. customThe organic phase was removed
  4. extractionthe aqueous phase was extracted with CH2Cl2 (10×25 mL)
  5. washThe combined organic extracts were washed with brine (25 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-c37449ca234e4975aae96d63a3a34b3b
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09296743B2

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