Sodium Hydroxide → 2-(6-Bromobenzo[d]thiazol-2-yl)-N-(2-sulfamoylethyl)acetamide

HRID 877424ノート

反応式

HRID 877424 の反応式
[Br:1][C:2]1[CH:16]=[CH:15][C:5]2[N:6]=[C:7]([CH2:9][C:10]([O:12]CC)=O)[S:8][C:4]=2[CH:3]=1.[OH-].[Na+].Cl.[NH2:20][CH2:21][CH2:22][S:23]([NH2:26])(=[O:25])=[O:24].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1.O>[Br:1][C:2]1[CH:16]=[CH:15][C:5]2[N:6]=[C:7]([CH2:9][C:10]([NH:20][CH2:21][CH2:22][S:23](=[O:25])(=[O:24])[NH2:26])=[O:12])[S:8][C:4]=2[CH:3]=1

参加物

7

反応物 4

HCID 14798Sodium HydroxideHCID 30215492-Aminoethanesulphonamide monohydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21041509Ethyl 6-bromo-2-benzothiazoleacetate

生成物 1

HCID 899619482-(6-Bromobenzo[d]thiazol-2-yl)-N-(2-sulfamoylethyl)acetamide収率 45%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

Ethyl 2-(6-bromobenzo[d]thiazol-2-yl)acetate (described in WO2011/074560, 250 mg, 0.83 mmol) in THF (4 mL) was treated with sodium hydroxide (1N NaOH, 0.92 mL, 0.92 mmol). After 2 hours, the reaction mixture was concentrated to dryness under reduced pressure, and the residue was co-evaporated with toluene (5 mL), re-dissolved in DMF (4 mL), and treated with 2-aminoethanesulfonamide hydrochloride (201 mg, 1.30 mmol), TEA (1.2 mL, 8.3 mmol) and HATU (475 mg, 1.30 mmol). After 16 hours, the reaction mixture was diluted with water (20 mL), extracted with DCM (3×10 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was dissolved in DMF/methanol and purified using reverse phase HPLC (Phenomemenx Luna AXIA 5 micron C18, 21.2×100 mm, 30 to 100% B over 15 minutes with 10 minute hold time, solvent A: 90% water/ACN/0.1% TFA, solvent B:90% ACN/water/0.1% TFA, Flow rate 20 mL/min; detector at 254). The pooled fractions were lyophilized to Compound A1a, (170 mg, 45% yield) as a white solid. HPLC: RT=0.75 (LCMS Method O). MS (ES): m/z=379.7 [M+H]+. 1H NMR (400 MHz, DMF-d7) δ 8.40 (d, J=2.0 Hz, 1H), 7.92 (d, J=8.8 Hz, 1H), 7.69 (dd, J=8.8, 2.0 Hz, 1H), 6.97 (s, 2H), 3.82-3.61 (m, 2H), 3.46 (s, 3H), 3.33 (dd, J=7.9, 6.4 Hz, 3H).

後処理

  1. concentrationthe reaction mixture was concentrated to dryness under reduced pressure
  2. dissolutionre-dissolved in DMF (4 mL)
  3. waitAfter 16 hours
  4. extractionextracted with DCM (3×10 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in DMF/methanol
  8. custompurified
  9. customphase HPLC (Phenomemenx Luna AXIA 5 micron C18, 21.2×100 mm, 30 to 100% B over 15 minutes with 10 minute hold time, solvent A: 90% water/ACN/0.1% TFA, solvent B:90% ACN/water/0.1% TFA, Flow rate 20 mL/min; detector at 254)
  10. customRT=0.75 (LCMS Method O)

出典と根拠

ORDレコード
ord-f5b333792c0b4d05a310fb2fe27b34a2
出典データセット
uspto-grants-2015_03
特許番号
US08987314B2

反応ノート

読み込み中…