Water → (S)-tert-butyl 1-(N-(4-(3-hydroxy-3-methylbut-1-ynyl)-5-(isoquinolin-6-yl)thiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

HRID 2109729Notes

Reaction equation

HRID 2109729 reaction equation
Br[C:2]1[S:6][C:5]([N:7]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:8][C@@H:9]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[N:4][C:3]=1[C:36]#[C:37][C:38]([OH:41])([CH3:40])[CH3:39].[CH:42]1[C:51]2[C:46](=[CH:47][C:48](B(O)O)=[CH:49][CH:50]=2)[CH:45]=[CH:44][N:43]=1.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1>[OH:41][C:38]([CH3:40])([CH3:39])[C:37]#[C:36][C:3]1[N:4]=[C:5]([N:7]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:8][C@@H:9]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]([F:19])([F:18])[F:20])=[CH:15][CH:16]=2)[S:6][C:2]=1[C:48]1[CH:47]=[C:46]2[C:51](=[CH:50][CH:49]=1)[CH:42]=[N:43][CH:44]=[CH:45]2

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 44119669(Isoquinolin-6-yl)boronic acidHCID 57634127(S)-tert-butyl 1-(N-(5-bromo-4-(3-hydroxy-3-methylbut-1-ynyl)thiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

Product 1

HCID 57634058(S)-tert-butyl 1-(N-(4-(3-hydroxy-3-methylbut-1-ynyl)-5-(isoquinolin-6-yl)thiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamateYield 37%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

(S)-tert-butyl 1-(N-(5-bromo-4-(3-hydroxy-3-methylbut-1-ynyl)thiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.025 g, 0.038 mmol) was taken up in 1 mL of dioxane in a microwave safe tube. Isoquinolin-6-ylboronic acid (0.0098 g, 0.057 mmol), sodium carbonate, 2M in water (0.075 mL, 0.15 mmol), and tetrakistriphenylphosphine palladium(0) (0.0044 g, 0.0038 mmol) were added. The mixture was degassed with nitrogen and the tube was sealed. The tube was then heated to 120° C. in a Personal Chemistry microwave unit for 20 minutes. The mixture was diluted with 10 mL of EtOAc, washed with 5 mL of water and 5 mL of brine, and then dried over MgSO4. Filtration and concentration under reduced pressure, followed by flash chromatography on silica gel (pipette column, 25% to 70% EtOAc/hexanes), afforded (S)-tert-butyl 1-(N-(4-(3-hydroxy-3-methylbut-1-ynyl)-5-(isoquinolin-6-yl)thiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.010 g, 37% yield) as a white solid.

Workup

  1. customThe mixture was degassed with nitrogen
  2. customthe tube was sealed
  3. additionThe mixture was diluted with 10 mL of EtOAc
  4. washwashed with 5 mL of water and 5 mL of brine
  5. dry with materialdried over MgSO4
  6. filtrationFiltration and concentration under reduced pressure

Sources & evidence

ORD record
ord-ccebb06c86b7419d81845794203df0bd
Source dataset
uspto-grants-2009_04
Patent number
US07514566B2

Reaction notes

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