Hydrochloric Acid → HCID 178479249、化合物

HRID 1854339ノート

反応式

HRID 1854339 の反応式
C(OC(=O)[NH:7][C@H:8]1[CH2:13][CH2:12][C@@H:11]([C:14]([NH:16][NH:17][C:18]2[N:19]=[C:20]3[CH:26]=[CH:25][N:24](S(C4C=CC(C)=CC=4)(=O)=O)[C:21]3=[N:22][CH:23]=2)=O)[CH2:10][CH2:9]1)(C)(C)C.C(OC(N[C@@H]1CC[C@H](C(O)=O)CC1)=O)(C)(C)C.O=S(Cl)[Cl:57].C([O-])([O-])=O.[Na+].[Na+].Cl>CO.O1CCOCC1>[ClH:57].[C:14]1([C@@H:11]2[CH2:12][CH2:13][C@H:8]([NH2:7])[CH2:9][CH2:10]2)[N:19]2[C:20]3[CH:26]=[CH:25][NH:24][C:21]=3[N:22]=[CH:23][C:18]2=[N:17][N:16]=1

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 24386Thionyl ChlorideHCID 178427353HCID 178427353、化合物HCID 178453971HCID 178453971、化合物

生成物 1

HCID 178479249HCID 178479249、化合物

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

A round-bottomed flask was charged with cis-tert-butyl-4-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclohexylcarbamate (0.415 g, 0.785 mmol, prepared using A from cis-4-(tert-butoxycarbonylamino)cyclohexanecarboxylic acid [AMRI] and Preparation #9), 1,4-dioxane (9 mL) and SOCl2 (0.115 mL, 1.57 mmol). The resulting mixture was heated at about 90° C. for about 1 h and then allowed to cool to ambient temperature. To the reaction mixture was added aqueous Na2CO3 (5 N, 7.85 mL, 15.7 mmol) and the reaction mixture was heated at about 90° C. for about 5 h. MeOH (5 mL) was added to the reaction mixture and the resulting mixture was heated at about 90° C. for about 16 h and then allowed to cool to ambient temperature. The layers were separated and the organic layer was concentrated under reduced pressure. To the residue was added 1,4-dioxane (10 mL) followed by HCl (4 M in 1,4-dioxane, 5 mL, 20.0 mmol). The resulting suspension was heated at about 60° C. for about 1 h and then allowed to cool to ambient temperature. The solid was collected by vacuum filtration, washed first with 1,4-dioxane (1 mL) then Et2O (50 mL) to yield the crude product cis-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclohexanamine hydrochloride (0.42 g, 98%, 84% purity). A portion of the crude HCl salt (0.075 g) was further purified by RP-HPLC (Table 2, Method g) to give cis-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclohexanamine (0.044 g) with 3 equiv NH4OAc as an excipient. LC/MS (Table 2, Method a) Rt=0.92 min; MS m/z: 257 (M+H)+.

後処理

  1. customprepared
  2. temperatureto cool to ambient temperature
  3. temperaturethe reaction mixture was heated at about 90° C. for about 5 h
  4. temperaturethe resulting mixture was heated at about 90° C. for about 16 h
  5. temperatureto cool to ambient temperature
  6. customThe layers were separated
  7. concentrationthe organic layer was concentrated under reduced pressure
  8. additionTo the residue was added 1,4-dioxane (10 mL)
  9. temperatureThe resulting suspension was heated at about 60° C. for about 1 h
  10. temperatureto cool to ambient temperature
  11. filtrationThe solid was collected by vacuum filtration
  12. washwashed first with 1,4-dioxane (1 mL)

出典と根拠

ORDレコード
ord-4bf48a9d3c0c4975820ed6ec126927f5
出典データセット
uspto-grants-2015_02
特許番号
US08962629B2

反応ノート

読み込み中…