Chloroacetyl chloride → HCID 87546374, compound

HRID 1435702Notes

Reaction equation

HRID 1435702 reaction equation
CS(O[CH2:6][CH2:7][C:8]1[N:9]=[C:10]([NH:13][S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=2[CH3:24])(=[O:16])=[O:15])[S:11][CH:12]=1)(=O)=O.[C:25]([NH:32][CH2:33][CH2:34][NH2:35])(OC(C)(C)C)=[O:26].CCN(C(C)C)C(C)C.[Cl:45][CH2:46]C(Cl)=O>C(O)C.C(Cl)Cl.CN(C1C=CN=CC=1)C>[ClH:23].[NH2:35][CH2:34][CH2:33][N:32]([CH2:6][CH2:7][C:8]1[N:9]=[C:10]([NH:13][S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=2[CH3:24])(=[O:15])=[O:16])[S:11][CH:12]=1)[C:25](=[O:26])[CH2:46][Cl:45]

Participants

8

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 187201N-BOC-ethylenediamineHCID 87545953HCID 87545953, compound

Product 1

HCID 87546374HCID 87546374, compoundYield 79.7%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of EXAMPLE 191A (600 mg, 1.46 mmol), N-BOC-ethylenediamine (469 mg, 2.93 mmol) and DIEA (189 mg, 1.46 mmol) was refluxed in ethanol (10 mL) for 3 h. The solvent was evaporated and the residue was flash chromatographed on SiO2 eluting with 10% methanol in DCM affording 265 mg (38%) intermediate tert-butyl 2-{[2-(2-{[(3-chloro-2-methylphenyl)sulfonyl]amino}-1,3-thiazol-4-yl)ethyl]amino}ethylcarbamate. This material (255 mg, 0.54 mmol) was dissolved in DCM (4 mL), followed by the addition of DMAP (163 mg, 1.21 mmol). Chloroacetyl chloride (134 mg, 1.18 mmol) dissolved in DCM (2 mL) was added, and the mixture was stirred for 1 h at room temperature followed by a wash with aqueous HCl (2 M). The remaining organic phase was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was taken up in ethyl acetate (25 mL), and at 0° C. HCl gas was bubbled trough under a period of 3 minutes. The mixture was stirred for 10 minutes and the solvent was evaporated giving 284 mg of N-(2-aminoethyl)-2-chloro-N-[2-(2-{[(3-chloro-2-methylphenyl)sulfonyl]amino}-1,3-thiazol-4-yl)ethyl]acetamide hydrochloride. This material (280 mg, 0.57 mmol) and sodium bicarbonate (169 mg, 2.01 mmol) were refluxed in ethanol (30 mL) for 2 h. The solvent was evaporated and the residue was flash chromatographed on RP silica gel gradient eluting with (acetonitrile in H2O/1% conc. HCl) giving 113 mg (47%) of 3-chloro-2-methyl-N-{4-[2-(2-oxo-1-piperazinyl)ethyl]-1,3-thiazol-2-yl}benzenesulfonamide hydrochloride.

Workup

  1. customThe solvent was evaporated
  2. customchromatographed on SiO2 eluting with 10% methanol in DCM affording 265 mg (38%) intermediate tert-butyl 2-{[2-(2-{[(3-chloro-2-methylphenyl)sulfonyl]amino}-1,3-thiazol-4-yl)ethyl]amino}ethylcarbamate
  3. additionwas added
  4. washa wash with aqueous HCl (2 M)
  5. dry with materialThe remaining organic phase was dried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customat 0° C
  9. customHCl gas was bubbled trough under a period of 3 minutes
  10. stirringThe mixture was stirred for 10 minutes
  11. customthe solvent was evaporated

Sources & evidence

ORD record
ord-9b15929da4084b9b896cf80d6dd26a87
Source dataset
uspto-grants-2009_11
Patent number
US07618961B2

Reaction notes

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