Dichloromethane → HCID 86613775, compound

HRID 661105Notes

Reaction equation

HRID 661105 reaction equation
C(Cl)Cl.[NH2:4][C@@H:5]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[C:26]([O:34]C)[CH:25]=1)[CH2:6][NH:7][C:8]1[S:9][C:10]([C:13]2[CH:22]=[C:21]3[C:16]([CH:17]=[CH:18][N:19]=[CH:20]3)=[CH:15][CH:14]=2)=[CH:11][N:12]=1.B(Br)(Br)Br>>[NH2:4][C@H:5]([CH2:6][NH:7][C:8]1[S:9][C:10]([C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:13]=2)[CH:20]=[N:19][CH:18]=[CH:17]3)=[CH:11][N:12]=1)[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:31])[F:32])=[C:26]([OH:34])[CH:25]=1.[NH2:4][C@H:5]([CH2:6][NH:7][C:8]1[S:9][C:10]([C:13]2[CH:22]=[C:21]3[C:16]([CH:17]=[CH:18][N:19]=[CH:20]3)=[CH:15][CH:14]=2)=[CH:11][N:12]=1)[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:32])([F:33])[F:31])=[C:26]([OH:34])[CH:25]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 25134Boron tribromideHCID 86613776HCID 86613776, compound

Product 2

HCID 57634192HCID 57634192, compoundHCID 86613775HCID 86613775, compoundYield 94.2%

Conditions

Temperature
-78 °C

Procedure

To a 50 mL round-bottomed flask was added anhydrous DCM (25 mL, 383 mmol) and N—((S)-2-amino-3-(3-methoxy-4-(trifluoromethyl)phenyl)-propyl)-5-(isoquinolin-7-yl)thiazol-2-amine (0.040 g, 0.086 mmol). The suspension was stirred at −78° C. and treated drop wise via syringe with boron tribromide (0.082 mL, 0.86 mmol). The solution was stirred at −78° C. for 1 hour and warmed to −12° C. and stirred for 1 hour and then stirred for 3 hours at room temperature. The reaction was quenched with NaHCO3 and ether, and the separated aqueous layer was extracted with ether (3×50 mL). The combined organic layers were washed with saturated sodium chloride, dried over Na2SO4, and concentrated to give the crude residue which was purified with flash column chromatography ((5%→20% MeOH in DCM) to obtain the desired product as an off white solid of 5-((S)-2-amino-3-(5-(isoquinolin-7-yl)thiazol-2-ylamino)propyl)-2-(trifluoromethyl)phenol (0.018 g, 46% yield). m/z (%): 445.4 (100%, M++H).

Workup

  1. stirringThe solution was stirred at −78° C. for 1 hour
  2. temperaturewarmed to −12° C.
  3. stirringstirred for 1 hour
  4. stirringstirred for 3 hours at room temperature
  5. customThe reaction was quenched with NaHCO3 and ether
  6. extractionthe separated aqueous layer was extracted with ether (3×50 mL)
  7. washThe combined organic layers were washed with saturated sodium chloride
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customto give the crude residue which
  11. customwas purified with flash column chromatography ((5%→20% MeOH in DCM)

Sources & evidence

ORD record
ord-39c5a1c393ed41329cb7578dc2792d93
Source dataset
uspto-grants-2011_12
Patent number
US08084479B2

Reaction notes

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