Potassium Carbonate → (2S,4S)-1-{N-[2-[4-(1,1-dioxidoisothiazolidin-2-yl) phenyl]hexahydro-2,5-methanopentalen-3a(1H)-yl]glycyl}-4-fluoropyrrolidine-2-carbonitrile

HRID 1015547노트

반응식

HRID 1015547 반응식
[O:1]=[S:2]1(=[O:23])[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:12]=[CH:11][C:10]([C:13]23[CH2:21][CH:17]4[CH2:18][CH:19]([CH2:20]2)[C:15]([NH2:22])([CH2:16]4)[CH2:14]3)=[CH:9][CH:8]=1.C([O-])([O-])=O.[K+].[K+].Cl[CH2:31][C:32]([N:34]1[CH2:38][C@@H:37]([F:39])[CH2:36][C@H:35]1[C:40]#[N:41])=[O:33]>CS(C)=O.CCOC(C)=O>[O:1]=[S:2]1(=[O:23])[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:8]=[CH:9][C:10]([C:13]23[CH2:21][CH:17]4[CH2:16][C:15]([NH:22][CH2:31][C:32]([N:34]5[CH2:38][C@@H:37]([F:39])[CH2:36][C@H:35]5[C:40]#[N:41])=[O:33])([CH2:14]2)[CH:19]([CH2:18]4)[CH2:20]3)=[CH:11][CH:12]=1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 57518632(2S,4S)-1-(2-Chloroacetyl)-4-fluoropyrrolidine-2-carbonitrileHCID 670178591-[4-(1,1-Dioxidoisothiazolidin-2-yl) phenyl]tricyclo[3.3.1.03,7]nonan-3-amine

생성물 1

HCID 24853220(2S,4S)-1-{N-[2-[4-(1,1-dioxidoisothiazolidin-2-yl) phenyl]hexahydro-2,5-methanopentalen-3a(1H)-yl]glycyl}-4-fluoropyrrolidine-2-carbonitrile수율 37%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 8857Ethyl Acetate용매

실험 절차

To a stirred mixture of 1-[4-(1,1-dioxidoisothiazolidin-2-yl)phenyl]tricyclo[3.3.1.03,7]nonan-3-amine (as obtained in example 8 Step II) (0.17 g, 0.5 mmol) and K2CO3 (0.21 g, 1.5 mmol) in DMSO (2 mL) at an ice bath temperature was added (2S,4S)-1-(chloroacetyl)-4-fluoropyrrolidine-2-carbonitrile (0.1 g, 0.5 mmol). The reaction mixture was gradually warmed to room temperature and stirred for 3 h. Upon completion of the reaction (checked by TLC), the reaction mixture was diluted with EtOAc and washed with water and brine, dried over Na2SO4, and the solvent was removed under reduced pressure. The crude product was purified by column chromatography to obtain (2S,4S)-1-{N-[2-[4-(1,1-dioxidoisothiazolidin-2-yl)phenyl]hexahydro-2,5-methanopentalen-3a(1H)-yl]glycyl}-4-fluoropyrrolidine-2-carbonitrile as an off-white powder (0.09 g) in 37% yield as a 3:1 mixture of two rotomers. IR cm−1 3438, 2953, 2776, 1673, 1518, 1427, 1301, 1135, 1078, 955; m/z (M+1) 487; 1H NMR (CDCl3) 300 MHz δ 7.25 (d, J=6.2 Hz, 2H), 7.20 (d, J=8.6 Hz, 2H), 5.42 (d (br), J=51.0 Hz, 0.8H), 5.34 (d (br), J=50.4 Hz, 0.2H), 5.15 (d, J=10.2 Hz, 0.2H), 4.98 (d, J=7.4 Hz, 0.8H), 4.0-3.50 (m, 4H), 3.76 (t, J=6.5H, 2H), 3.35 (t, J=6.5 Hz, 2H), 2.80-2.28 (m, 6H), 2.15-1.58 (m, 10H).

후처리

  1. customUpon completion of the reaction (checked by TLC)
  2. washwashed with water and brine
  3. dry with materialdried over Na2SO4
  4. customthe solvent was removed under reduced pressure
  5. customThe crude product was purified by column chromatography

출처 및 근거

ORD 기록
ord-e1cfa7a197854268a3009b3cb9452fb5
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07985759B2

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