Hydrochloric Acid → 1-(4-Methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)ethanamine dihydrochloride salt

HRID 57402Notes

Reaction equation

HRID 57402 reaction equation
C(=O)C.[CH3:4][C:5]1[N:6]=[C:7]([C:23](=O)[CH3:24])[S:8][C:9]=1[C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]([CH3:22])([CH3:21])[C:17]([F:20])([F:19])[F:18])[CH:11]=1.[BH3-]C#[N:28].[Na+].CCO.[ClH:33]>O1CCOCC1>[ClH:33].[ClH:33].[CH3:4][C:5]1[N:6]=[C:7]([CH:23]([NH2:28])[CH3:24])[S:8][C:9]=1[C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]([CH3:22])([CH3:21])[C:17]([F:20])([F:19])[F:18])[CH:11]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 5003444Sodium cyanoborohydrideHCID 131736955HCID 131736955, compound

Product 1

HCID 904140411-(4-Methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)ethanamine dihydrochloride salt

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

1-(4-methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)ethanone ethanone (1.6 g, 4.87 mmol), NH4OAc (5.6 g, 73.1 mmol), and NaBH3CN (1.2 g, 19.5 mmol) were taken up in 40 mL 200 proof EtOH, and heated at 130 C for 10 minutes in a sealed tube. The mixture was concentrated to remove the EtOH. Crude was taken up in 50 ml water+50 mL EtOAc. 6N NaOH was added until aqueous pH was ˜9. Separated layers, and extracted aqueous with EtOAc (50 ml). The combined organic layer was washed with 60 mL brine and dried with Na2SO4. Filtered and concentrated with reduced pressure to give 1.58 g crude tan oil. This material was taken up in 20 mL dioxane. 2.2 eq HCl (4N in dioxane) was added, and stirred 1 h. Yellow ppt was formed. The suspension was concentrated in vacuo to give 1.97 g 1-(4-methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)ethanamine dihydrochloride salt as a yellow-green solid, which was carried forward without further purification. Major product Anal. RP-HPLC tR=1.23 min. MS m/z 330.1 (M+H)+.

Workup

  1. temperatureheated at 130 C for 10 minutes in a sealed tube
  2. concentrationThe mixture was concentrated
  3. customto remove the EtOH
  4. addition6N NaOH was added until aqueous pH was ˜9
  5. extractionSeparated layers, and extracted aqueous with EtOAc (50 ml)
  6. washThe combined organic layer was washed with 60 mL brine
  7. dry with materialdried with Na2SO4
  8. filtrationFiltered
  9. concentrationconcentrated with reduced pressure
  10. customto give 1.58 g crude tan oil
  11. customYellow ppt was formed
  12. concentrationThe suspension was concentrated in vacuo

Sources & evidence

ORD record
ord-d9c606d14f9746499aeeffc92f8c795d
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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