2-Aminothiazole → 1-chloro-N-(thiazol-2-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)isoquinoline-6-sulfonamide

HRID 1473390ノート

反応式

HRID 1473390 の反応式
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[NH2:6].[CH3:7][Si:8]([CH2:11][CH2:12][O:13][CH2:14]Cl)([CH3:10])[CH3:9].[Cl:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([S:27](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:29])=[O:28])=[CH:24][CH:25]=2)[CH:20]=[CH:19][N:18]=1.CC(C)([O-])C.[Li+]>CC#N.O>[Cl:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([S:27]([N:6]([C:2]3[S:1][CH:5]=[CH:4][N:3]=3)[CH2:14][O:13][CH2:12][CH2:11][Si:8]([CH3:7])([CH3:9])[CH3:10])(=[O:29])=[O:28])=[CH:24][CH:25]=2)[CH:20]=[CH:19][N:18]=1

参加物

7

反応物 4

HCID 21552-AminothiazoleHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 86687382Perfluorophenyl 1-chloroisoquinoline-6-sulfonate

生成物 1

HCID 866874321-chloro-N-(thiazol-2-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)isoquinoline-6-sulfonamide収率 39.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6342Acetonitrile溶媒

実験手順

A solution of thiazol-2-amine (0.134 g, 1.342 mmol) in 3 mL MeCN was treated with SEM-Cl (0.238 ml, 1.342 mmol) and was allowed to stir at room temperature for 30 minutes. LC/MS showed mostly product, so the reaction mixture was treated with perfluorophenyl 1-chloroisoquinoline-6-sulfonate (See, Example 73, Step 1; 0.500 g, 1.220 mmol) and was cooled to −10° C. Lithium tert-butoxide (1N in THF) (2.441 ml, 2.441 mmol) was added, and the reaction mixture was allowed to warm to room temperature overnight. The reaction mixture was poured into water and was extracted with DCM. The organics were dried over MgSO4 and concentrated. Purification of the crude residue by silica gel column chromatography (0 to 100% EtOAc/heptane) gave 1-chloro-N-(thiazol-2-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)isoquinoline-6-sulfonamide (0.220 g, 0.482 mmol, 39.5% yield). m/z (ESI) 456.0 (M+H)+;

後処理

  1. temperaturewas cooled to −10° C
  2. temperatureto warm to room temperature overnight
  3. extractionwas extracted with DCM
  4. dry with materialThe organics were dried over MgSO4
  5. concentrationconcentrated
  6. customPurification of the crude residue by silica gel column chromatography (0 to 100% EtOAc/heptane)

出典と根拠

ORDレコード
ord-d7acd598d19945e49bcf96bfdc6a1c6f
出典データセット
uspto-grants-2015_04
特許番号
US09012443B2

反応ノート

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