Ammonia → US11401286, Example 135

HRID 1508805ノート

反応式

HRID 1508805 の反応式
[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

参加物

4

反応物 2

HCID 222Ammonia2 回HCID 90338478ethyl 2-(4-((2-(3-hydroxycyclopentyl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)amino)phenyl)acetate

生成物 1

HCID 90110206US11401286, Example 135収率 67%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
100 °C

実験手順

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 B, 0.056 g, 0.147 mmol), methanol (3 mL) and ammonia (4.2 mL, 7N in methanol, 29.4 mmol). The vial was sealed and the resulting mixture was stirred at 100° C. for 23 h. LCMS analysis of the cooled reaction showed ˜66% 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. The cooled reaction mixture solution was concentrated under reduced pressure. The residue was absorbed on silica (4 g) then purified by chromatography on silica using dichloromethane/(80:20:1 dichloromethane/methanol/conc. NH4OH) (10:0 to 0:10) as the eluent to afford the title compound (0.034 g, 67%) as an off-white solid. MW=351.44. M.p. 93-95° C. 1H NMR (DMSO-d6, 500 MHz) δ 7.95 (s, 1H), 7.42 (s, 1H), 7.24-7.20 (m, 2H), 7.13-7.09 (m, 2H), 6.85 (br s, 1H), 6.64 (s, 1H), 5.60 (br s, 1H), 4.13-4.07 (m, 1H), 3.33 (s, 2H), 3.03 (quin, J=7.7 Hz, 1H), 2.78 (t, J=7.5 Hz, 2H), 2.74 (t, J=7.0 Hz, 2H), 2.09-1.98 (m, 3H), 1.95-1.86 (m, 1H), 1.77-1.56 (m, 4H). MS: APCI, m/z 352 [M+H]+.

後処理

  1. customThe vial was sealed
  2. customLCMS analysis of the cooled reaction
  3. temperaturethe mixture was heated at 100° C. for 2 h
  4. customThe cooled reaction mixture solution
  5. concentrationwas concentrated under reduced pressure
  6. customThe residue was absorbed on silica (4 g)
  7. customthen purified by chromatography on silica

出典と根拠

ORDレコード
ord-f6b14c1286ad44efb64640b247763d9b
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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