Trifluoroacetic acid → (S)-N-(6-Cyano-1-thiazol-5-ylmethyl-1,2,3,4-tetrahydro-quinolin-3-yl)-benzenesulfonamide

HRID 1363084Notes

Reaction equation

HRID 1363084 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH2:8][C@@H:7]([NH:13][S:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(=[O:16])=[O:15])[CH2:6]2)#[N:2].[S:23]1[C:27]([CH:28]=O)=[CH:26][N:25]=[CH:24]1.C(O)(C(F)(F)F)=O.[SiH](CC)(CC)CC>C(Cl)Cl>[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:28][C:27]1[S:23][CH:24]=[N:25][CH:26]=1)[CH2:8][C@@H:7]([NH:13][S:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(=[O:16])=[O:15])[CH2:6]2)#[N:2]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 27735771,3-Thiazole-5-carbaldehydeHCID 66757946(S)-N-(6-Cyano-1,2,3,4-tetrahydro-quinolin-3-yl)-benzenesulfonamide

Product 1

HCID 11304426(S)-N-(6-Cyano-1-thiazol-5-ylmethyl-1,2,3,4-tetrahydro-quinolin-3-yl)-benzenesulfonamideYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1G (94 mg, 0.3 mmol) and thiazole-5-carbaldehyde (67.9 mg, 0.6 mmol) (prepared following the procedures described in Alessandro Dondoni, et al, Synthesis, 11, 998-1001, (1987)) in a mixed solvents of TFA (0.75 mL) and CH2Cl2 (0.75 mL) was added Et3SiH (0.096 mL, 0.6 mmol). The resulting mixture was stirred at RT under argon for 18 h, then concentrated under reduced pressure. The residue was diluted with saturated aqueous NaHCO3, then extracted with EtOAc (3×20 mL). The combined EtOAc extracts were washed with brine, dried (Na2SO4), and concentrated. The resulting residue was chromatographed (silica gel) eluting with EtOAc (50-90%) in hexane to give the title compound as an off-white solid (70 mg, 57%). HPLC: 99% at 5.43 min (retention time) (Conditions: Zorbax SB C18 (4.6×75 mm); Eluted with 0% to 100% B, 8 min gradient (A 90% H2O—10% MeOH—0.1% H3PO4 and B=10% H2O−90% MeOH−0.1% H3PO4), Flow rate at 2.5 mL/min, UV detection at 220 nm). MS (ES): m/z 411 [M+H]+; Chiral HPLC 100% e.e.; retention time=32.9 min; Conditions: AD (4.6×250 mm); Eluted with 40% isopropanol in hexane for 50 min at 1 mL/min.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue was diluted with saturated aqueous NaHCO3
  3. extractionextracted with EtOAc (3×20 mL)
  4. washThe combined EtOAc extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe resulting residue was chromatographed (silica gel)
  8. washeluting with EtOAc (50-90%) in hexane

Sources & evidence

ORD record
ord-26d2c3aa68b042579e78c87144472c65
Source dataset
uspto-grants-2011_02
Patent number
US07884113B2

Reaction notes

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