Hydrochloric Acid → Zamicastat

HRID 526720

反応式

HRID 526720 の反応式
[CH2:1]([NH:8][C:9](=O)[CH2:10][C:11]1[N:12]([C@@H:17]2[CH2:26][C:25]3[C:20](=[C:21]([F:28])[CH:22]=[C:23]([F:27])[CH:24]=3)[O:19][CH2:18]2)[C:13](=[S:16])[NH:14][CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+].O1CCCC1.B(F)(F)F.Cl.[OH-].[Na+]>O1CCCC1>[CH2:1]([NH:8][CH2:9][CH2:10][C:11]1[N:12]([C@@H:17]2[CH2:26][C:25]3[C:20](=[C:21]([F:28])[CH:22]=[C:23]([F:27])[CH:24]=3)[O:19][CH2:18]2)[C:13](=[S:16])[NH:14][CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

7

反応物 5

HCID 313Hydrochloric Acid2 回HCID 14798Sodium HydroxideHCID 71088Boron, trifluoro(tetrahydrofuran)-, (T-4)-HCID 4311764Sodium borohydrideHCID 71153280HCID 71153280、化合物

生成物 1

HCID 25052630Zamicastat収率 76%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of (R)—N-benzyl-2-(3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl)acetamide (16.62 g, 40 mmol) in tetrahydrofuran (133 ml) was added sodium borohydride (3.78 g, 100 mmol). The suspension was then cooled to 0° C. and a solution of boron trifluoride tetrahydrofuran (14.56 ml, 132 mmol) in tetrahydrofuran (85 ml). The mixture was warmed up to room temperature (20-25° C.) and stirred for 24 hours. After cooling to 0° C., 1N hydrochloric acid (64 ml, 64 mmol), pH to 1 with 6N hydrochloric acid (17.7 ml, 108 mmol), and the mixture was refluxed for 30 min. Tetrahydrofuran was removed under reduced pressure. The precipitate was collected, washed with water (50 mL). The wet solid was suspended in a mixture of methanol (250 ml) and water (38 ml). The suspension was heated to reflux until complete dissolution; 1N sodium hydroxide (45 ml, 48 mmol) was added (pH 8-9). The crystallization occurred at approx 50° C. The suspension was cooled to 15° C., aged for 3 hours. The precipitate was collected, washed with methanol (33 mL), dried in vacuum at 50° C. to give (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione (12.5 g, 30.01 mmol, 76% yield).

後処理

  1. temperatureThe mixture was warmed up to room temperature (20-25° C.)
  2. temperatureAfter cooling to 0° C.
  3. customTetrahydrofuran was removed under reduced pressure
  4. customThe precipitate was collected
  5. washwashed with water (50 mL)
  6. additionThe wet solid was suspended in a mixture of methanol (250 ml) and water (38 ml)
  7. temperatureThe suspension was heated
  8. temperatureto reflux until complete dissolution
  9. customThe crystallization
  10. customoccurred at approx 50° C
  11. temperatureThe suspension was cooled to 15° C.
  12. waitaged for 3 hours
  13. customThe precipitate was collected
  14. washwashed with methanol (33 mL)
  15. customdried in vacuum at 50° C.

出典と根拠

ORDレコード
ord-e16b6e859dc74defb449b8539e69d11b
出典データセット
uspto-grants-2016_05
特許番号
US09346751B2

関連ノート

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