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Hydrochloric Acid → 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide hydrochloride

HRID 2200866
ノート
印刷プレビュー

反応式

HRID 2200866 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[O:29][CH3:30])[CH2:5][NH:6][C:7]1[C:12]([C:13]([NH:15][CH2:16][C:17]2[N:22]=[CH:21][CH:20]=[CH:19][N:18]=2)=[O:14])=[CH:11][N:10]=[C:9](S(C)=O)[N:8]=1.C(N(CC)CC)C.Cl.[CH:39]12[CH2:44][CH:43]1[CH2:42][NH:41][CH2:40]2.Cl>C1COCC1.CO>[ClH:1].[CH:39]12[CH2:44][CH:43]1[CH2:42][N:41]([C:9]1[N:8]=[C:7]([NH:6][CH2:5][C:4]3[CH:26]=[CH:27][C:28]([O:29][CH3:30])=[C:2]([Cl:1])[CH:3]=3)[C:12]([C:13]([NH:15][CH2:16][C:17]3[N:22]=[CH:21][CH:20]=[CH:19][N:18]=3)=[O:14])=[CH:11][N:10]=1)[CH2:40]2
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 223352893-Azabicyclo[3.1.0]hexane hydrochlorideHCID 86342163Avanafil Impurity K

生成物 1

HCID 1183083252-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide hydrochloride収率 72.4%

試薬・触媒・溶媒 2

HCID 887
Methanol
溶媒
HCID 8028Tetrahydrofuran溶媒

実験手順

In absolute anhydrous THF (10 mL) was dissolved 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylsulfinyl)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide (100 mg, 0.22 mmol). Triethylamine (0.22 g, 2.2 mmol) was added dropwisely, and 3-azabicyclo[3.1.0]hexan hydrochloride salt (42 mg, 0.35 mmol) was added. The reaction mixture was heated to reflux overnight. The solvent was removed by rotary evaporation, and water was added, followed by extraction with DCM. The organic phase was dried over sodium sulfate and purified by silica gel column chromatography (DCM/methanol=20/1 to 10/1) to give a solid. The solid was dissolved in methanol (0.05 mL), and hydrochloric acid (1 mol/L) was added. The solvent was removed to give 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide hydrochloride (40 mg, 39% yield).

後処理

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux overnight
  3. customThe solvent was removed by rotary evaporation, and water
  4. additionwas added
  5. extractionfollowed by extraction with DCM
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. custompurified by silica gel column chromatography (DCM/methanol=20/1 to 10/1)
  8. customto give a solid
  9. customThe solvent was removed

出典と根拠

ORDレコード
ord-e4e56d2831754b1481fcdc8987a2c0b0
出典データセット
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09359371B2

反応ノート

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