Diisopropylethylamine → Methyl 2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-methoxybenzo[d]thiazole-6-carboxylate

HRID 1748204Notes

Reaction equation

HRID 1748204 reaction equation
Cl[C:2]1[S:3][C:4]2[CH:10]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:8]=[C:7]([O:15][CH3:16])[C:5]=2[N:6]=1.[CH:17]12[NH:24][CH:21]([CH2:22][CH2:23]1)[CH2:20][CH:19]([O:25][CH2:26][C:27]1[C:28]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[O:41][C:42]([F:45])([F:44])[F:43])=[N:29][O:30][C:31]=1[CH:32]1[CH2:34][CH2:33]1)[CH2:18]2.C(N(C(C)C)CC)(C)C>CC(N(C)C)=O.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>[CH:32]1([C:31]2[O:30][N:29]=[C:28]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[O:41][C:42]([F:43])([F:44])[F:45])[C:27]=2[CH2:26][O:25][CH:19]2[CH2:18][CH:17]3[N:24]([C:2]4[S:3][C:4]5[CH:10]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:8]=[C:7]([O:15][CH3:16])[C:5]=5[N:6]=4)[CH:21]([CH2:22][CH2:23]3)[CH2:20]2)[CH2:33][CH2:34]1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 67981000HCID 67981000, compoundHCID 67983256HCID 67983256, compound

Product 1

HCID 59053602Methyl 2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-methoxybenzo[d]thiazole-6-carboxylateYield 53.3%

Reagents, catalysts & solvents 3

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
120 °C

Procedure

The ester, methyl 2-chloro-4-methoxybenzo[d]thiazole-6-carboxylate (124 mg, 0.48 mmol) and 4-((8-azabicyclo[3.2.1]octan-3-yloxy)methyl)-5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole (200 mg, 0.48 mmol) and diisopropylethylamine (0.1 mL, 0.7 mmol) were sequentially dissolved in dimethylacetamide (1 mL) and heated to 120° C. overnight. The reaction mixture was allowed to cool to room temperature and then diluted with ethyl acetate and aqueous saturated sodium bicarbonate solution. The organics were separated, the aqueous layer was subjected to a further wash with ethyl acetate, and the organics were combined and dried (MgSO4) then evaporated in vacuo. The product was purified by silica gel chromatography with a gradient of 0-100% ethyl acetate/hexanes to furnish 161 mg of a clear oil that was used directly in the following transformation without further manipulation.

Workup

  1. temperatureto cool to room temperature
  2. customThe organics were separated
  3. washa further wash with ethyl acetate
  4. dry with materialdried (MgSO4)
  5. customthen evaporated in vacuo
  6. customThe product was purified by silica gel chromatography with a gradient of 0-100% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-73649a9275c34657b9e832229d2aaf32
Source dataset
uspto-grants-2015_10
Patent number
US09150568B2

Reaction notes

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