Phenol → (7-Methoxynaphthalen-2-yl)sulfonic acid {1-[1-amino-7-isoquinolinylmethyl]-2-oxopyrrolidin-3-(S)-yl}amide hydrochloride

HRID 394599

反応式

HRID 394599 の反応式
C1(O)C=CC=CC=1.[Cl:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:19][N:20]3[CH2:24][CH2:23][C@H:22]([NH:25][S:26]([C:29]4[CH:38]=[CH:37][C:36]5[C:31](=[CH:32][C:33]([O:39][CH3:40])=[CH:34][CH:35]=5)[CH:30]=4)(=[O:28])=[O:27])[C:21]3=[O:41])[CH:17]=2)[CH:12]=[CH:11][N:10]=1.C([O-])(=O)C.[NH4+:46]>CCOCC>[ClH:8].[NH2:46][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:19][N:20]3[CH2:24][CH2:23][C@H:22]([NH:25][S:26]([C:29]4[CH:38]=[CH:37][C:36]5[C:31](=[CH:32][C:33]([O:39][CH3:40])=[CH:34][CH:35]=5)[CH:30]=4)(=[O:28])=[O:27])[C:21]3=[O:41])[CH:17]=2)[CH:12]=[CH:11][N:10]=1

参加物

5

反応物 3

HCID 996PhenolHCID 517165Ammonium Acetate2 回HCID 155458317-Methoxy-naphthalene-2-sulfonic acid[1-(1-chloro-isoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(s)-yl]-amide

生成物 1

HCID 70124326(7-Methoxynaphthalen-2-yl)sulfonic acid {1-[1-amino-7-isoquinolinylmethyl]-2-oxopyrrolidin-3-(S)-yl}amide hydrochloride収率 53.5%

試薬・触媒・溶媒 1

HCID 3283Diethyl Ether溶媒

反応条件

温度
115 °C

実験手順

In a round-bottomed flask fitted with a cold finger condenser, phenol (0.569 g, 6 mmol) and 7-methoxy-naphthalene-2-sulfonic acid [1-(1-chloro-isoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]-amide (0.2 g, 0.4 mmol) is melted at 70° C. The mixture is stirred for 5 minutes, then ammonium acetate (0.462 g, 6 mmol) is added and heated at 115° C. for 2 hours. After this time, additional ammonium acetate (0.462 g, 6 mmol) is added. After 2 hours the reaction mixture is cooled to room temperature then partitioned between EtOAc and 0.5N NaOH, The organic layer is separated and washed with water and brine, then dried over Na2SO4, filtered and concentrated. The resulting residue is partially purified by RP-HPLC eluting with a gradient of 10% CH3CN/H2O (0.1% TFA) to 100% CH3CN. The appropriate fractions are concentrated in vacuo. The solid which precipitates out from the solution is then filtered, dried and purified again by column chromatography eluting with 5% MeOH/CH2Cl2. This product is then triturated with cold MeOH and the collected solid is suspended in MeOH and cooled to 0° C. HCl(g) is bubbled through the slurry for a few minutes during which time all the solid dissolves into the solution. The solvent is removed in vacuo and the title product (0.11 g, 0.214 mmol) is washed with ether and dried.

後処理

  1. customIn a round-bottomed flask fitted with a cold finger condenser
  2. temperatureAfter 2 hours the reaction mixture is cooled to room temperature
  3. customthen partitioned between EtOAc and 0.5N NaOH
  4. customThe organic layer is separated
  5. washwashed with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue is partially purified by RP-HPLC
  10. washeluting with a gradient of 10% CH3CN/H2O (0.1% TFA) to 100% CH3CN
  11. concentrationThe appropriate fractions are concentrated in vacuo
  12. customThe solid which precipitates out from the solution
  13. filtrationis then filtered
  14. customdried
  15. custompurified again by column chromatography
  16. washeluting with 5% MeOH/CH2Cl2
  17. customThis product is then triturated with cold MeOH
  18. temperaturecooled to 0° C
  19. customHCl(g) is bubbled through the slurry for a few minutes during which time all the solid
  20. dissolutiondissolves into the solution
  21. customThe solvent is removed in vacuo

出典と根拠

ORDレコード
ord-d6e8712fe9b14041ba023cb7ca6bd364
出典データセット
uspto-grants-2003_08
特許番号
US06602864B1

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