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

HRID 1483211

反応式

HRID 1483211 の反応式
[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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-abcd82fd2efd45838ddf252bc4d8f693
出典データセット
uspto-grants-2016_08
特許番号
US09416141B2

関連ノート

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