Benzenemethanamine, 3,4-dichloro- → n-(3,4-Dichlorobenzyl)-4-[(1,3-thiazol-2-ylamino)sulfonyl]benzamide

HRID 401748

反応式

HRID 401748 の反応式
COC1C=C(OC)C=CC=1C[N:6]([C:19]1[S:20][CH:21]=[CH:22][N:23]=1)[S:7]([C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][CH:11]=1)(=[O:9])=[O:8].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.C(Cl)Cl.[Cl:64][C:65]1[CH:66]=[C:67]([CH:70]=[CH:71][C:72]=1[Cl:73])[CH2:68][NH2:69]>>[Cl:64][C:65]1[CH:66]=[C:67]([CH:70]=[CH:71][C:72]=1[Cl:73])[CH2:68][NH:69][C:14](=[O:16])[C:13]1[CH:12]=[CH:11][C:10]([S:7]([NH:6][C:19]2[S:20][CH:21]=[CH:22][N:23]=2)(=[O:8])=[O:9])=[CH:18][CH:17]=1

参加物

6

反応物 5

HCID 1608Benzenemethanamine, 3,4-dichloro-HCID 6344DichloromethaneHCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 577319334-{[(2,4-Dimethoxybenzyl)(1,3-thiazol-2-yl)amino]sulfonyl}benzoic acid

生成物 1

HCID 57732208n-(3,4-Dichlorobenzyl)-4-[(1,3-thiazol-2-ylamino)sulfonyl]benzamide収率 98.3%

実験手順

4-{[(2,4-Dimethoxybenzyl)(1,3-thiazol-2-yl)amino]sulfonyl}benzoic acid (Preparation 99, 1.30E3 mg, 0.00300 mol), HBTU (1400.8 mg, 0.0031671 mol) and Et3N (1.07 mL, 0.00766 mol) were mixed in methylene chloride (10 mL, 0.2 mol). 3,4-dichlorobenzylamine (457.3 mg, 0.002598 mol) was added and the reaction stirred overnight. The reaction was washed with saturated sodium bicarbonate (aq). The organic phase was separated and dried over magnesium sulfate, the solvent was removed in vacuo to give an oily residue. The residue was purified by column chromatography (40 g silica gel column, hexanes to 50% ethyl acetate-hexanes gradient elution). Product fractions were combined and evaporated to give 1.13 g of the protected benzamide intermediate. The residue was dissolved in DCM and TFA was added dropwise until wet pH paper turned acidic when held above the reaction. After 30 minutes of stirring at room temperature, the solid precipitate was collected by filtration. The solid was rinsed with DCM, then ethyl ether. The solid was dissolved in 0.5N NaOH (5 mL) and filtered. The filtrate was washed 2× with ethyl ether, then treated with activated carbon and filtered through Celite. The pale yellow filtrate was acidified to pH 2 with 6N HCl. The white precipitate was collected by filtration and rinsed with water then ethyl ether. Vacuum drying yielded 446 mg of product as a white powder.

後処理

  1. washThe reaction was washed with saturated sodium bicarbonate (aq)
  2. customThe organic phase was separated
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent was removed in vacuo
  5. customto give an oily residue
  6. customThe residue was purified by column chromatography (40 g silica gel column, hexanes to 50% ethyl acetate-hexanes gradient elution)
  7. customevaporated

出典と根拠

ORDレコード
ord-239d373ca51c48749ba32f6b86c57b5b
出典データセット
uspto-grants-2014_06
特許番号
US08741934B2

関連ノート

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