Triethylamine → 6-Ethyl-2-[3-(6-fluoronaphthalen-2-yl)ureido]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide

HRID 1483211

반응식

HRID 1483211 반응식
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7](C(O)=O)[CH:6]=[CH:5]2.C([N:17]([CH2:20]C)CC)C.P(N=[N+]=[N-])(=O)(OC1C=CC=CC=1)[O:23]C1C=CC=CC=1.[NH2:41][C:42]1[S:52][C:45]2[CH2:46][N:47]([CH2:50][CH3:51])[CH2:48][CH2:49][C:44]=2[C:43]=1[C:53]([NH2:55])=[O:54]>C1(C)C=CC=CC=1.O1CCCC1>[CH2:50]([N:47]1[CH2:48][CH2:49][C:44]2[C:43]([C:53]([NH2:55])=[O:54])=[C:42]([NH:41][C:20]([NH:17][C:7]3[CH:6]=[CH:5][C:4]4[C:9](=[CH:10][CH:11]=[C:2]([F:1])[CH:3]=4)[CH:8]=3)=[O:23])[S:52][C:45]=2[CH2:46]1)[CH3:51]

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 123414Diphenylphosphoryl azideHCID 6144392-Amino-6-ethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamideHCID 27827886-Fluoro-2-naphthoic acid

생성물 1

HCID 1182697006-Ethyl-2-[3-(6-fluoronaphthalen-2-yl)ureido]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide수율 22%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
80 °C

실험 절차

To a stirred mixture of 6-fluoro-2-naphthoic acid (G1, 0.951 g, 5.00 mmol), triethylamine (0.759 g, 7.50 mmol) in anhydrous toluene (40 mL) was added diphenyl phosphorazidate (1.51 g, 5.50 mmol). After addition, the reaction mixture was heated at 80° C. for 2 h and then cooled to room temperature. The resulting solution was added to another stirred solution of compound F4 (1.13 g, 5.00 mmol) in anhydrous tetrahydrofuran (50 mL). After addition, the resulting mixture was heated at 80° C. for another 2 h. After this time, the reaction mixture was cooled to room temperature, quenched with saturated aqueous sodium bicarbonate (60 mL), and extracted with ethyl acetate (3×100 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel eluting with methanol/methylene chloride (15:85) to afford compound G2 as an off-white solid (451 mg, 22%): 1H NMR (300 MHz, DMSO-d6) δ 11.01 (s, 1H), 10.27 (s, 1H), 8.19 (d, J=1.8 Hz, 1H), 7.91 (dd, J=10.8 and 5.7 Hz, 1H), 7.84 (d, J=9.0 Hz, 1H), 7.64-6.70 (m, 5H), 3.47 (s, 2H), 2.78 (d, J=5.1 Hz, 2H), 2.66 (d, J=5.1 Hz, 2H), 2.55-2.49 (m, 2H), 1.08 (t, J=7.0 Hz, 3H). MS (M+H) 413.

후처리

  1. additionAfter addition
  2. temperaturecooled to room temperature
  3. additionAfter addition
  4. temperaturethe resulting mixture was heated at 80° C. for another 2 h
  5. temperatureAfter this time, the reaction mixture was cooled to room temperature
  6. customquenched with saturated aqueous sodium bicarbonate (60 mL)
  7. extractionextracted with ethyl acetate (3×100 mL)
  8. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting residue was purified by flash column chromatography on silica gel eluting with methanol/methylene chloride (15:85)

출처 및 근거

ORD 기록
ord-abcd82fd2efd45838ddf252bc4d8f693
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09416141B2

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