Dichloromethane → (R)-9-(4-(1-Aminopropan-2-yl)phenyl)-8-methoxy-2,6-dimethylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

HRID 1853824Notes

Reaction equation

HRID 1853824 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]([CH3:13])[C:10]2[N:9](COCC[Si](C)(C)C)[C:8](=[O:22])[C:7]3[S:23][C:24]([CH3:26])=[CH:25][C:6]=3[C:5]=2[C:4]=1[C:27]1[CH:32]=[CH:31][C:30]([C@@H:33]([CH3:43])[CH2:34][NH:35]C(=O)OC(C)(C)C)=[CH:29][CH:28]=1.FC(F)(F)C(O)=O.C(Cl)[Cl:52]>>[ClH:52].[NH2:35][CH2:34][C@@H:33]([C:30]1[CH:29]=[CH:28][C:27]([C:4]2[C:5]3[C:6]4[CH:25]=[C:24]([CH3:26])[S:23][C:7]=4[C:8](=[O:22])[NH:9][C:10]=3[C:11]([CH3:13])=[CH:12][C:3]=2[O:2][CH3:1])=[CH:32][CH:31]=1)[CH3:43]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 67449401(R)-tert-Butyl 2-(4-(8-methoxy-2,6-dimethyl-4-oxo-5-((2-(trimethylsilyl)ethoxy)methyl)-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate

Product 1

HCID 86689508(R)-9-(4-(1-Aminopropan-2-yl)phenyl)-8-methoxy-2,6-dimethylthieno[2,3-c]quinolin-4(5H)-one hydrochlorideYield 30%

Procedure

To a solution of (R)-tert-butyl 2-(4-(8-methoxy-2,6-dimethyl-4-oxo-5-((2-(trimethylsilyl)ethoxy)methyl)-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (24 mg, 0.039 mmol) in CH2Cl2 (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, 30%) 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, 1.1H), 3.29-3.18 (m, 3H), 2.63 (s, 3H), 1.47 (d, J=6.1 Hz, 3H): ESI MS m/z 392 [C23H24N2O4S+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-9282a8a75e59499898242bc5e9571a04
Source dataset
uspto-grants-2015_02
Patent number
US08962648B2

Reaction notes

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