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

HRID 1799084ノート

反応式

HRID 1799084 の反応式
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

参加物

7

反応物 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、化合物

生成物 1

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

試薬・触媒・溶媒 2

HCID 64052-Methyl-2-butanol溶媒HCID 21226129Dichloromethane methanol溶媒

反応条件

温度
80 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-c57a2fff2d6f40b6a4d82ec9296558f4
出典データセット
uspto-grants-2013_01
特許番号
US08344008B2

反応ノート

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