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

HRID 1473390Notes

Reaction equation

HRID 1473390 reaction equation
[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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

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)+;

Workup

  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)

Sources & evidence

ORD record
ord-d7acd598d19945e49bcf96bfdc6a1c6f
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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