Boron tribromide → HCID 16743585, compound

HRID 1993626Notes

Reaction equation

HRID 1993626 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]([NH:30][C:31]2[S:32][C:33]([CH3:40])=[C:34]([C:36]([F:39])([F:38])[F:37])[N:35]=2)([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][C:3]=1[O:41]C.B(Br)(Br)Br>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]([C:16]2[CH:21]=[C:20]([O:22][C:23]([F:27])([F:28])[CH:24]([F:26])[F:25])[CH:19]=[C:18]([F:29])[CH:17]=2)([NH:30][C:31]2[S:32][C:33]([CH3:40])=[C:34]([C:36]([F:38])([F:37])[F:39])[N:35]=2)[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:4][C:3]=1[OH:41]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 16743584HCID 16743584, compound

Product 1

HCID 16743585HCID 16743585, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-76 °C

Procedure

To a solution of (S)-N-(1-(4-fluoro-3-methoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-5-methyl-4-(trifluoromethyl)thiazol-2-amine (28.5 mg, 0.046 mmol) in CH2Cl2 (1 mL) at −76° C. was added BBr3 (460 μL, 1 M in DCM, 0.46 mmol). The reaction mixture was stirred at −76° C. for 2 h and quenched by the addition of MeOH. The reaction mixture was concentrated and the residue was purified by preparative HPLC Phenomenex Luna AXIA S5 30×100 mm Ballistic column 50-100% MeOH (90% in water, 0.1% TFA) gradient over 10 min with flow rate 40 mL/min and UV detection at 220 nm. (S)-2-fluoro-5-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(5-methyl-4-(trifluoromethyl)thiazol-2-ylamino)-2-phenylethyl)phenol eluted at a retention time of 11.09 min and was isolated as a colorless gum (20 mg, 72% yield). LCMS: RT=4.12 min [M+H] 607.2 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm). NMR: 400 MHz 1H (CDCl3) 7.14 ppm, 3H, m; 6.95 ppm, 6H, m; 6.65 ppm, 2H, m; 6.07 ppm, 1H, s; 5.88 ppm, 1H, m; 3.69 ppm, 2H, d, J=1.26 Hz; 3.49 ppm, 1H, s; 2.29 ppm, 3H, q, J=2.19 Hz.

Workup

  1. customquenched by the addition of MeOH
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue was purified by preparative HPLC Phenomenex Luna AXIA
  4. wait30×100 mm Ballistic column 50-100% MeOH (90% in water, 0.1% TFA) gradient over 10 min with flow rate 40 mL/min and UV detection at 220 nm
  5. wash(S)-2-fluoro-5-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(5-methyl-4-(trifluoromethyl)thiazol-2-ylamino)-2-phenylethyl)phenol eluted at a retention time of 11.09 min

Sources & evidence

ORD record
ord-1c1af6a7471943e1ada901e18173e951
Source dataset
uspto-grants-2010_01
Patent number
US07652023B2

Reaction notes

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