Boron tribromide → HCID 86689511, compound

HRID 1853829Notes

Reaction equation

HRID 1853829 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]C)=[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.B(Br)(Br)Br>C(Cl)Cl>[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[OH:31])=[CH:15][CH:16]=1)[CH3:30]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 67448021HCID 67448021, compound

Product 1

HCID 86689511HCID 86689511, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (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 (60 mg, 0.096 mmol) in CH2Cl2 (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, 1.7 Hz, 1H), 7.46 (dd, J=7.8, 1.8 Hz, 1H), 7.32 (dd, J=23.9, 7.9 Hz, 2H), 7.10 (s, 1H), 5.46 (d, J=2.9 Hz, 1H), 3.28-3.15 (m, 3H), 2.55 (s, 3H), 1.49 (d, J=6.3 Hz, 3H); ESI MS m/z 383 [C21H19FN2O2S+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-243c6d7cfaa04439abb300ad6e6a6dd0
Source dataset
uspto-grants-2015_02
Patent number
US08962648B2

Reaction notes

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