Ammonia → US11401286, Example 135

HRID 1508804노트

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HRID 1508804 반응식
[OH:1][CH:2]1[CH2:6][CH2:5][CH:4]([C:7]2[N:12]=[C:11]3[CH2:13][CH2:14][CH2:15][C:10]3=[C:9]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][C:24]([O:26]CC)=O)=[CH:19][CH:18]=3)[CH:8]=2)[CH2:3]1.[NH3:29]>CO>[OH:1][CH:2]1[CH2:6][CH2:5][CH:4]([C:7]2[N:12]=[C:11]3[CH2:13][CH2:14][CH2:15][C:10]3=[C:9]([NH:16][C:17]3[CH:18]=[CH:19][C:20]([CH2:23][C:24]([NH2:29])=[O:26])=[CH:21][CH:22]=3)[CH:8]=2)[CH2:3]1

참가 물질

4

반응물 2

HCID 222Ammonia2회HCID 90338478ethyl 2-(4-((2-(3-hydroxycyclopentyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)amino)phenyl)acetate

생성물 1

HCID 90110206US11401286, Example 135수율 25%

시약·촉매·용매 1

HCID 887Methanol용매

반응 조건

온도
100 °C

실험 절차

A 10-mL vial was charged with ethyl 2-(4-((2-(3-hydroxycyclopentyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)amino)phenyl)acetate (diastereomer A, 0.022 g, 0.058 mmol), methanol (2 mL) and ammonia (1.7 mL, 7N in methanol, 11.5 mmol). The vial was sealed and the resulting mixture was stirred at 100° C. for 23 h. After this time, LCMS analysis of the cooled reaction showed ˜88% conversion. Additional ammonia (1.0 mL, 7N in methanol, 7.0 mmol) was added and the mixture was heated at 100° C. for 2 h. Then, the cooled reaction mixture was concentrated under reduced pressure. The residue was absorbed on silica (2 g) and purified by chromatography on silica using dichloromethane/(80:20:1 dichloromethane/methanol/conc. NH4OH) (10:0 to 0:10) as eluent to afford the title compound (0.005 g, 25%) as a light brown solid. MW=351.44 1H NMR (DMSO-d6, 500 MHz) δ 7.86 (s, 1H), 7.41 (s, 1H), 7.23-7.19 (m, 2H), 7.12-7.08 (m, 2H), 6.84 (br s, 1H), 6.60 (s, 1H), 4.39 (d, J=4.0 Hz, 1H), 4.25-4.20 (m, 1H), 3.33 (s, 2H), 3.18 (quin, J=6.5 Hz, 1H), 2.78 (t, J=7.5 Hz, 2H), 2.73 (t, J=7.5 Hz, 2H), 2.05-1.88 (m, 4H), 1.83-1.72 (m, 2H), 1.67-1.56 (m, 1H), 1.53-1.45 (m, 1H); APCI m/z 352 [M+H]+.

후처리

  1. customThe vial was sealed
  2. customAfter this time, LCMS analysis of the cooled reaction
  3. temperaturethe mixture was heated at 100° C. for 2 h
  4. customThen, the cooled reaction mixture
  5. concentrationwas concentrated under reduced pressure
  6. customThe residue was absorbed on silica (2 g)
  7. custompurified by chromatography on silica

출처 및 근거

ORD 기록
ord-df32144cac68434ea6e961bc22760a79
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221843B2

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