Hydrochloric Acid → 6-(7-(4-(3-Cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)nicotinic acid

HRID 1253582노트

반응식

HRID 1253582 반응식
[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH:29]=[CH:28][C:27]([CH:30]=[O:31])=[CH:26][N:25]=5)[S:23][C:16]=34)=[C:10]([F:32])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1.[OH:33]OS([O-])=O.[K+].Cl>CN(C=O)C>[CH:1]1([NH:4][C:5](=[O:6])[NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH:29]=[CH:28][C:27]([C:30]([OH:33])=[O:31])=[CH:26][N:25]=5)[S:23][C:16]=34)=[C:10]([F:32])[CH:9]=2)[CH2:2][CH2:3]1

참가 물질

5

반응물 3

HCID 313Hydrochloric AcidHCID 23707502Potassium hydroxy sulfiteHCID 582365791-Cyclopropyl-3-(3-fluoro-4-(2-(5-formylpyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea

생성물 1

HCID 674418286-(7-(4-(3-Cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)nicotinic acid수율 80%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
50 °C

실험 절차

To a suspension of aldehyde 47 (200 mg, 0.446 mmol) in DMF (10 mL) was added Oxone® (330 mg, 0.535 mmol) at RT and the reaction mixture was stirred at 50° C. for 16 hours. The reaction mixture was cooled to 0° C., treated with 1N aqueous HCl (20 mL) and stirred at RT for an additional hour. The resultant precipitate was collected by filtration, washed with water (30 mL) and dried. The crude product was triturated with MeOH to afford title compound 225 (165 mg, 80% yield) as a beige solid. NMR (400 MHz, CD3OD) δ (ppm): 9.66 (bs, 1H), 8.98 (dd, J=1.9, 0.9 Hz, 1H), 8.51 (d, J=5.5 Hz, 1H), 8.31 (s, 1H), 8.22 (dd, J=8.1, 1.9 Hz, 1H), 8.17 (dd, J=8.1, 0.9 Hz, 1H), 7.77 (dd, J=13.7, 2.5 Hz, 1H), 7.45 (bs, 1H), 7.37 (t, J=9.1 Hz, 1H), 7.26 (dd, J=8.9, 1.5 Hz, 1H), 6.62 (d, J=5.3, 0.8 Hz, 1H), 2.60-2.52 (m, 1H), 0.69-0.56 (m, 2H), 0.50-0.37 (m, 2H). [Carboxylic OH is not seen]. MS: 465.3 (MH)+

후처리

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. stirringstirred at RT for an additional hour
  3. filtrationThe resultant precipitate was collected by filtration
  4. washwashed with water (30 mL)
  5. customdried
  6. customThe crude product was triturated with MeOH

출처 및 근거

ORD 기록
ord-455ca91b799e4e838e2d92c1f6d1fa1c
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08455484B2

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