Potassium Carbonate → 5-{2-[4-(4-Methyl-benzothiazol-2-yloxy)-phenyl]-ethyl}-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid amide

HRID 384532노트

반응식

HRID 384532 반응식
Cl.[CH2:2]1[CH:6]2[CH2:7][NH:8][CH2:9][CH:5]2[CH2:4][N:3]1[C:10]([NH2:12])=[O:11].[CH2:13]1C2CNCC2CN1C(N)=O.C([O-])([O-])=O.[K+].[K+].CS([CH2:34][CH2:35][C:36]1[CH:52]=[CH:51][C:39]([O:40][C:41]2[S:42][C:43]3[CH:49]=[C:48](C)[CH:47]=[CH:46][C:44]=3[N:45]=2)=[CH:38][CH:37]=1)(=O)=O>C(Cl)Cl.CO.C(O)(CC)(C)C>[CH3:13][C:46]1[C:44]2[N:45]=[C:41]([O:40][C:39]3[CH:38]=[CH:37][C:36]([CH2:35][CH2:34][N:8]4[CH2:7][CH:6]5[CH2:2][N:3]([C:10]([NH2:12])=[O:11])[CH2:4][CH:5]5[CH2:9]4)=[CH:52][CH:51]=3)[S:42][C:43]=2[CH:49]=[CH:48][CH:47]=1

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 57448388Hexahydropyrrolo[3,4-c]pyrrole-2(1h)-carboxamide hydrochlorideHCID 57448389Hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid amideHCID 67206214HCID 67206214, 화합물

생성물 1

HCID 425976575-{2-[4-(4-Methyl-benzothiazol-2-yloxy)-phenyl]-ethyl}-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid amide수율 5%

시약·촉매·용매 2

HCID 64052-Methyl-2-butanol용매HCID 21226129Dichloromethane methanol용매

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온도
80 °C

실험 절차

A solution of hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid amide hydrochloride in 50% CH2Cl2/CH3OH was treated with DOWEX Monosphere 550A (OH) anion-exchange resin to afford the free base. The DOWEX resin was filtered and the resulting solution was concentrated and used without further purification. To a solution of this hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid amide (85 mg, 0.54 mmol) and K2CO3 (116 mg, 0.84 mmol) in tert-amyl alcohol (2.6 mL) was added 2-[4-(2-methanesulfonyl-ethyl)-phenoxy]-6-methyl-benzothiazole (120 mg, 0.34 mmol). The reaction mixture was heated to 80° C. for 16 h. The reaction mixture was filtered and washed with CH3OH. The resulting liquid was purified by preparative reverse phase HPLC to afford the title compound (11 mg, 5%). MS (ESI): mass calcd. for C23H26N4O2S, 422.55; m/z found, 423.2 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.62 (d, J=8.3 Hz, 1H), 7.48 (s, 1H), 7.28 (s, 4H), 7.20 (dd, J=8.3, 1.1 Hz, 1H), 4.39 (s, 2H), 3.60 (dd, J=10.2, 8.2 Hz, 2H), 3.30 (dd, J=10.0, 1.9 Hz, 2H), 2.98-2.87 (m, 2H), 2.86-2.80 (m, 2H), 2.76 (dd, J=9.3, 6.9 Hz, 2H), 2.74-2.67 (m, 2H), 2.53 (dd, J=9.3, 3.4 Hz, 2H), 2.45 (s, 3H).

후처리

  1. customto afford the free base
  2. filtrationThe DOWEX resin was filtered
  3. concentrationthe resulting solution was concentrated
  4. customused without further purification
  5. filtrationThe reaction mixture was filtered
  6. washwashed with CH3OH
  7. customThe resulting liquid was purified by preparative reverse phase HPLC

출처 및 근거

ORD 기록
ord-6bf6d45f4fd548579908aa21b9b3b883
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08367719B2

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