Ammonia → US11401286, Example 133

HRID 1508796ノート

反応式

HRID 1508796 の反応式
C(O[C:4](=[O:34])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13]2[CH:18]=[C:17]([C:19]3[N:20](C(OC(C)(C)C)=O)[CH:21]=[CH:22][CH:23]=3)[N:16]=[C:15]3[CH2:31][CH2:32][CH2:33][C:14]=23)=[CH:8][CH:7]=1)C.[NH3:35]>CO>[NH:20]1[CH:21]=[CH:22][CH:23]=[C:19]1[C:17]1[N:16]=[C:15]2[CH2:31][CH2:32][CH2:33][C:14]2=[C:13]([NH:12][C:9]2[CH:8]=[CH:7][C:6]([CH2:5][C:4]([NH2:35])=[O:34])=[CH:11][CH:10]=2)[CH:18]=1

参加物

4

反応物 2

HCID 222AmmoniaHCID 90338568tert-butyl 2-(4-((4-(2-ethoxy-2-oxoethyl)phenyl)amino)-6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)-1H-pyrrole-1-carboxylate

生成物 1

HCID 90338445US11401286, Example 133収率 38%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
100 °C

実験手順

A 20-mL vial was charged with tert-butyl 2-(4-((4-(2-ethoxy-2-oxoethyl)phenyl)amino)-6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)-1H-pyrrole-1-carboxylate (0.110 g, 0.24 mmol, 1.0) and methanol (3 mL). To this solution was added NH3 (6.8 mL, 7N in methanol, 476 mmol). The vial was sealed and the resulting mixture was stirred at 100° C. for 65 h. After this time, the crude reaction solution was concentrated under reduced pressure. The residue was adsorbed onto silica then purified by chromatography on silica using dichloromethane/(90:10:0.25 dichloromethane/methanol/aq. NH4OH) (10:0 to 0:10) as eluent followed by preparative HPLC (water/acetonitrile with 0.05% TFA) to afford 2-(4-((2-(1H-pyrrol-2-yl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)amino)phenyl)acetamide (0.030 g, 38%) as a brown solid. MW=332.40. 1H NMR (DMSO-d6, 500 MHz) δ 11.16 (br s, 1H), 7.93 (br s, 1H), 7.42 (br s, 1H), 7.26-7.22 (m, 2H), 7.17-7.13 (m, 2H), 7.03 (s, 1H), 6.85 (s, 1H), 6.74-6.71 (m, 1H), 6.39 (s, 1H), 6.05-6.20 (m, 1H), 3.34 (s, 2H), 2.86 (t, J=7.5 Hz, 2H), 2.78 (t, J=7.5 Hz, 2H), 2.05 (quin, J=7.5 Hz, 2H). MS: ESI, m/z 333 [M+H]+. Treatment with 1.25M HCl in methanol afforded the title compound (0.035 g, 100%) as an off-white solid. MW=368.86. M.p. 163-165° C. 1H NMR (DMSO-d6, 500 MHz) δ 13.43 (br s, 1H), 12.06 (br s, 1H), 9.46 (br s, 1H), 7.52 (br s, 1H), 7.40-7.36 (m, 2H), 7.32-7.28 (m, 2H), 7.12-7.09 (m, 1H), 7.08 (s, 1H), 7.06-7.03 (m, 1H), 6.92 (br s, 1H), 6.29-6.25 (m, 1H), 3.43 (s, 2H), 3.11 (t, J=7.5 Hz, 2H), 2.87 (t, J=7.5 Hz, 2H), 2.20 (quin, J=7.5 Hz, 2H); APCI MS m/z 333 [M+H]+.

後処理

  1. customThe vial was sealed
  2. customAfter this time, the crude reaction solution
  3. concentrationwas concentrated under reduced pressure
  4. customthen purified by chromatography on silica

出典と根拠

ORDレコード
ord-455d4aed5e8f4fea8c8fe5ce48f7d091
出典データセット
uspto-grants-2015_12
特許番号
US09221843B2

反応ノート

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