Ammonia → US11401286, Example 133

HRID 1508796노트

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HRID 1508796 반응식
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

참가 물질

4

반응물 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

생성물 1

HCID 90338445US11401286, Example 133수율 38%

시약·촉매·용매 1

HCID 887Methanol용매

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온도
100 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-455d4aed5e8f4fea8c8fe5ce48f7d091
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221843B2

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