Hydrochloric Acid → (S)-2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxy-N-(4-(N-thiazol-2-ylsulfamoyl)phenyl) butanamide

HRID 1696154Notes

Reaction equation

HRID 1696154 reaction equation
C[Al](C)C.CCCCCC.[CH:11]1[C:16]([NH2:17])=[CH:15][CH:14]=[C:13]([S:18]([NH:21][C:22]2[S:26][CH:25]=[CH:24][N:23]=2)(=[O:20])=[O:19])[CH:12]=1.[Cl:27][C:28]1[CH:29]=[C:30]2[C:35](=[CH:36][CH:37]=1)[N:34]([C@H:38]1[CH2:42][CH2:41][O:40][C:39]1=[O:43])[CH2:33][CH2:32][CH2:31]2.Cl>ClCCl.C(OC(=O)C)C>[Cl:27][C:28]1[CH:29]=[C:30]2[C:35](=[CH:36][CH:37]=1)[N:34]([C@@H:38]([CH2:42][CH2:41][OH:40])[C:39]([NH:17][C:16]1[CH:11]=[CH:12][C:13]([S:18](=[O:20])(=[O:19])[NH:21][C:22]3[S:26][CH:25]=[CH:24][N:23]=3)=[CH:14][CH:15]=1)=[O:43])[CH2:33][CH2:32][CH2:31]2

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 5340SulfathiazoleHCID 8058HexaneHCID 16682925TrimethylaluminumHCID 59465621(S)-3-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)dihydrofuran-2(3H)-one

Product 1

HCID 53627656(S)-2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxy-N-(4-(N-thiazol-2-ylsulfamoyl)phenyl) butanamideYield 30%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Prepared using general procedure 58. Under an N2 atmosphere at RT, 2M-trimethylaluminium in hexane (19.2 mL, 38.4 mmol) was added drop wise to a stirring solution of sulfathiazole (9.81 g, 38.4 mmol) in dichloromethane (90 mL) in 30 minutes. Upon completion of addition, the mixture was stirred at RT for an hour. Added (S)-3-(6-chloro-3,4-dihyroquinolin-1-(2H)-yl)dihydrofuran-2-(3H)-one (10.7 g, 42.7 mol) in dichloromethane (90 mL) to above solution over 30 minutes. The mixture was stirred for 16 hrs at RT. The reaction mixture was diluted with 500 mL of ethylacetate were added. The aqueous phase was acidified to pH 2 with an (1N) aqueous HCl solution. The ethyl acetate layer was washed with (1N) aqueous HCl (3×200 mL) till LCMS showed disappearance of sulfathiazole. The organic layer was dried over MgSO4, filtered, concentrated. Purification via silica gel chromatography using 2-10% methanol in dichloromethane gave the (S)-2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxy-N-(4-(N-thiazol-2-ylsulfamoyl)phenyl) butanamide as a white solid (5.73 g, 30% yield). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=507.3; tR=1.53 min. 1H NMR (400 MHz, DMSO-d6) δ 10.38 (s, 1H), 7.78 (s, 4H), 7.24 (d, J=4.6 Hz, 1H), 7.01-6.96 (m, 2H), 6.82-6.76 (m, 2H), 4.68 (s, 1H), 4.59 (t, J=7.1 Hz, 1H), 4.03 (dd, J=14.2, 7.1 Hz, 1H), 3.47 (s, 2H), 3.35-3.21 (m, 2H), 2.69 (t, J=6.0 Hz, 2H), 2.14-2.06 (m, 1H), 1.93-1.78 (m, 2H).

Workup

  1. customPrepared
  2. additionUpon completion of addition
  3. stirringThe mixture was stirred for 16 hrs at RT
  4. additionwere added
  5. washThe ethyl acetate layer was washed with (1N) aqueous HCl (3×200 mL) till LCMS
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-78c51a3df594427fadee702f4f4aa0e5
Source dataset
uspto-grants-2012_04
Patent number
US08163720B2

Reaction notes

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