Trifluoroacetic acid → HCID 67449342, compound

HRID 1853828Notes

Reaction equation

HRID 1853828 reaction equation
[F:1][C:2]1[S:43][C:5]2[C:6](=[O:42])[N:7](COCC[Si](C)(C)C)[C:8]3[C:9]([CH3:33])=[CH:10][C:11]([O:31][CH3:32])=[C:12]([C:14]4[CH:19]=[CH:18][C:17]([C@@H:20]([CH3:30])[CH2:21][NH:22]C(=O)OC(C)(C)C)=[CH:16][CH:15]=4)[C:13]=3[C:4]=2[CH:3]=1.FC(F)(F)C(O)=O>>[NH2:22][CH2:21][C@@H:20]([C:17]1[CH:18]=[CH:19][C:14]([C:12]2[C:13]3[C:4]4[CH:3]=[C:2]([F:1])[S:43][C:5]=4[C:6](=[O:42])[NH:7][C:8]=3[C:9]([CH3:33])=[CH:10][C:11]=2[O:31][CH3:32])=[CH:15][CH:16]=1)[CH3:30]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67448021HCID 67448021, compound

Product 1

HCID 67449342HCID 67449342, compoundYield 46.7%

Procedure

To a solution (R)-tert-butyl 2-(4-(2-fluoro-8-methoxy-6-methyl-4-oxo-5-((2-(trimethylsilyl)ethoxy)methyl)-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (17 mg, 0.027 mmol) in CH2C2 (1 mL) at rt was added trifluoroacetic acid (1.0 mL) and the reaction was stirred at that temperature for 2 h. The mixture was concentrated and the residue was dissolved methanol (2 mL) and treated with NH4OH (2 mL). The resulting mixture was stirred at rt for 2 h and purified by preparatory HPLC (C18 silica, acetonitrile/water (with 0.05% TFA) gradient). The desired fractions were combined, concentrated and the residue was dissolved in aqueous HCl, concentrated and dried under high vacuum to afford the desired product (5 mg, 43%) as a hydrochloride salt: 1H NMR (500 MHz, CD3OD) δ 7.52 (dd, J=7.8, 1.5 Hz, 1H), 7.47 (dd, J=7.7, 1.5 Hz, 1H), 7.32 (s, 1H), 7.31-7.22 (m, 2H), 5.30 (d, J=2.7 Hz, 1H), 3.29-3.18 (m, 3H), 2.63 (s, 3H), 1.47 (d, J=6.1 Hz, 3H): ESI MS m/z 397 [C22H21FN2O2S+H]+.

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionthe residue was dissolved methanol (2 mL)
  3. additiontreated with NH4OH (2 mL)
  4. stirringThe resulting mixture was stirred at rt for 2 h
  5. custompurified by preparatory HPLC (C18 silica, acetonitrile/water (with 0.05% TFA) gradient)
  6. concentrationconcentrated
  7. dissolutionthe residue was dissolved in aqueous HCl
  8. concentrationconcentrated
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-21d77458b436407baaa49eeee80b074f
Source dataset
uspto-grants-2015_02
Patent number
US08962648B2

Reaction notes

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