Diisopropylethylamine → N-[[2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-5-(2,6-dimethyl-4-pyridinyl)-4-thiazolyl]methyl]-3-methyl-5-isoxazolecarboxamide

HRID 473981Notes

Reaction equation

HRID 473981 reaction equation
C[CH2:2][N:3](C(C)C)C(C)C.[CH3:10][C@H:11]1[O:16][C@@H:15]([CH3:17])[CH2:14][N:13]([C:18]2[S:19][C:20]([C:25]3[CH:30]=[C:29]([CH3:31])[N:28]=[C:27]([CH3:32])[CH:26]=3)=[C:21](NC)[N:22]=2)[CH2:12]1.[CH3:33][C:34]1[CH:38]=[C:37]([C:39](Cl)=[O:40])[O:36][N:35]=1>C(Cl)Cl>[CH3:10][C@H:11]1[O:16][C@@H:15]([CH3:17])[CH2:14][N:13]([C:18]2[S:19][C:20]([C:25]3[CH:26]=[C:27]([CH3:32])[N:28]=[C:29]([CH3:31])[CH:30]=3)=[C:21]([CH2:2][NH:3][C:39]([C:37]3[O:36][N:35]=[C:34]([CH3:33])[CH:38]=3)=[O:40])[N:22]=2)[CH2:12]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 129050993-Methyl-1,2-oxazole-5-carbonyl chlorideHCID 67216071[2-(cis-2,6-Dimethyl-morpholin-4-yl)-5-(2,6-dimethyl-pyridin-4-yl)-thiazol-4-yl]-methylamine

Product 1

HCID 53237122N-[[2-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-5-(2,6-dimethyl-4-pyridinyl)-4-thiazolyl]methyl]-3-methyl-5-isoxazolecarboxamideYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

DIPEA (0.16 mL, 0.97 mmol) was added to a solution of Intermediate 5 (150 mg, 0.45 mmol) in DCM (6 mL). The reaction mixture was cooled to 0° C. under nitrogen atmosphere. 3-Methylisoxazole-5-carbonyl chloride (79 mg, 0.54 mmol) was then added dropwise and stirring was continued for 1 h at room temperature. The reaction was washed with sodium bicarbonate and then twice with water. The organic layer was dried over a magnesium sulphate plug and evaporated. The residue was purified by preparative HPLC (RP Shandon Hyperprep C18 BDS—8 μm, 250 g, 5 cm; mobile phase (0.25% NH4HCO3 solution in water, CH3CN)), yielding 127 mg (64%) of Compound 4.

Workup

  1. washThe reaction was washed with sodium bicarbonate
  2. dry with materialThe organic layer was dried over a magnesium sulphate plug
  3. customevaporated
  4. customThe residue was purified by preparative HPLC (RP Shandon Hyperprep C18 BDS—8 μm, 250 g, 5 cm; mobile phase (0.25% NH4HCO3 solution in water, CH3CN))

Sources & evidence

ORD record
ord-c37e071bf18a43a69220815a122cfa8e
Source dataset
uspto-grants-2014_01
Patent number
US08637510B2

Reaction notes

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