Hydrochloric Acid → 2-[5-(6-{2-[pyrrolidin-2-yl]-3H-imidazol-4-yl}-benzo[1,2-b:4,5-b']dithiophene-2-yl)-1H-imidazol-2-yl]-pyrrolidine tetrahydrochloride

HRID 72032

反応式

HRID 72032 の反応式
[NH:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[C:6]1[NH:10][C:9]([C:11]2[S:15][C:14]3[CH:16]=[C:17]4[CH:21]=[C:20]([C:22]5[NH:26][C:25]([CH:27]6[CH2:31][CH2:30][CH2:29][NH:28]6)=[N:24][CH:23]=5)[S:19][C:18]4=[CH:32][C:13]=3[CH:12]=2)=[CH:8][N:7]=1.[ClH:33]>C(O)C>[ClH:33].[ClH:33].[ClH:33].[ClH:33].[NH:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[C:6]1[NH:10][C:9]([C:11]2[S:15][C:14]3[CH:16]=[C:17]4[CH:21]=[C:20]([C:22]5[NH:26][C:25]([CH:27]6[CH2:31][CH2:30][CH2:29][NH:28]6)=[N:24][CH:23]=5)[S:19][C:18]4=[CH:32][C:13]=3[CH:12]=2)=[CH:8][N:7]=1

参加物

4

反応物 2

HCID 313Hydrochloric AcidHCID 666207262-[5-(6-{2-[pyrrolidin-2-yl]-3H-imidazol-4-yl}-benzo[1,2-b:4,5-b']dithiophene-2-yl)-1H-imidazol-2-yl]-pyrrolidine

生成物 1

HCID 666207252-[5-(6-{2-[pyrrolidin-2-yl]-3H-imidazol-4-yl}-benzo[1,2-b:4,5-b']dithiophene-2-yl)-1H-imidazol-2-yl]-pyrrolidine tetrahydrochloride

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

A solution of fully protected 2-[5-(6-{2-[pyrrolidin-2-yl]-3H-imidazol-4-yl}-benzo[1,2-b:4,5-b′]dithiophene-2-yl)-1H-imidazol-2-yl]-pyrrolidine (100 mg, 0.11 mmol), ethanol (4 mL) and concentrated HCl (1 mL) was heated to 60° C. for 16 hours. The reaction was concentrated and the crude material dissolved in DCM (10 mL). This solution was concentrated to yield crude 2-[5-(6-{2-[pyrrolidin-2-yl]-3H-imidazol-4-yl}-benzo[1,2-b:4,5-b′]dithiophene-2-yl)-1H-imidazol-2-yl]-pyrrolidine tetrahydrochloride. To this material was added a solution of 2-methoxycarbonylamino-3-methylbutyric acid (38 mg, 0.22 mmol) and HATU (83 mg, 0.22 mmol) in DMF (1.5 mL). To the resulting solution was added diisopropylethylamine (190 μL, 1.1 mmol). After stirring for 2 hours at room temperature, the reaction was concentrated and purified twice by preparative reverse phase HPLC (Gemini, 10 to 45% ACN/H2O+0.1% HCO2H). The product fractions were passed through a freebasing column (STRATOSPHERES™ PL-HCO3 MP SPE, Part #: PL3540-C603) and lyophilized to give (1-{2-[5-(6-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-benzo[1,2-b:4,5-b′]dithiophene-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (29 mg, 34%). LCMS-ESI+: calculated for C38H46N8O6S2: 774.95; observed [M+1]+: 775.96. 1H-NMR: 400 MHz, (CD3OD) δ: 8.16-8.11 (m, 2H), 7.49-7.47 (m, 2H), 7.38-7.29 (m, 2H), 5.18-5.15 (m, 2H), 4.24 (d, J=7.4 Hz, 2H), 4.04-3.96 (m, 2H), 3.91-3.86 (m, 2H), 3.66 (br s, 6H), 2.38-2.17 (m, 6H), 2.11-1.98 (m, 4H), 1.00-0.89 (m, 12H) ppm.

後処理

  1. concentrationThe reaction was concentrated
  2. dissolutionthe crude material dissolved in DCM (10 mL)
  3. concentrationThis solution was concentrated

出典と根拠

ORDレコード
ord-f0c11f6112ff4ebfbd4dc16655fde02a
出典データセット
uspto-grants-2014_09
特許番号
US08822430B2

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