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

HRID 1853825Notes

Reaction equation

HRID 1853825 reaction equation
C[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.B(Br)(Br)Br>>[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[OH:2])=[CH:32][CH:31]=1)[CH3:43]

Participants

3

Reactant 2

HCID 25134Boron tribromideHCID 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 67450224(R)-9-(4-(1-Aminopropan-2-yl)phenyl)-8-hydroxy-2,6-dimethylthieno[2,3-c]quinolin-4(5H)-one

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 (40 mg, 0.064 mmol) in CH2C2 (1 mL) at 0° C. was added BBr3 (1.0 M in methylene chloride, 1.0 mL, 1.0 mmol) and the reaction was stirred at that temperature for 1 h and quenched by pouring onto water or ice-water. The resulting 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 as a hydrochloride salt: 1H NMR (500 MHz, CD3OD) δ 7.55 (dd, J=7.9, 1.9 Hz, 1H), 7.45 (dd, J=7.7, 1.9 Hz, 1H), 7.34 (dd, J=7.9, 1.8 Hz, 1H), 7.28 (dd, J=7.7, 1.7 Hz, 1H), 7.06 (d, J=0.7 Hz, 1H), 5.70 (d, J=1.1 Hz, 1H), 3.29-3.13 (m, 3H), 2.55 (s, 3H), 2.30 (d, J=1.0 Hz, 3H), 1.50 (d, J=6.5 Hz, 3H); ESI MS m/z 378 [C22H22N2O2S+H]+.

Workup

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

Sources & evidence

ORD record
ord-28228d3b14cb4aadb4470d58be7b4c35
Source dataset
uspto-grants-2015_02
Patent number
US08962648B2

Reaction notes

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