Potassium Phosphate, Tribasic → Ethyl 5-[(tert-butoxycarbonyl)amino]-2-(6-morpholin-4-ylpyridin-3-yl)-1,3-thiazole-4-carboxylate

HRID 2060631Notes

Reaction equation

HRID 2060631 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[S:13][C:12](I)=[N:11][C:10]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:28]2[CH:29]=[CH:30][C:31]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[N:32][CH:33]=2)O1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[C:1]([O:5][C:6]([NH:8][C:9]1[S:13][C:12]([C:28]2[CH:33]=[N:32][C:31]([N:34]3[CH2:35][CH2:36][O:37][CH2:38][CH2:39]3)=[CH:30][CH:29]=2)=[N:11][C:10]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 27953634-(5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl)morpholineHCID 67306268Ethyl 5-((tert-butoxycarbonyl)amino)-2-iodothiazole-4-carboxylate

Product 1

HCID 67305664Ethyl 5-[(tert-butoxycarbonyl)amino]-2-(6-morpholin-4-ylpyridin-3-yl)-1,3-thiazole-4-carboxylate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Ethyl 5-[(tert-butoxycarbonyl)amino]-2-iodo-1,3-thiazole-4-carboxylate (1 g, 2.5 mmol), 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]morpholine (1.1 g, 3.7 mmol), Pd2(dba)3 (0.23 g, 0.25 mmol), and tricyclohexylphosphine (0.18 g, 0.63 mmol) were combined in a flask. The flask was evacuated and backfilled with argon three times. Fully degassed dioxane (17 mL) and 1.27 M aqueous potassium phosphate (6.5 ml, 8.3 mmol) were added sequentially. The reaction was heated to 100° C. for 6 h. The mixture was then cooled, diluted with ethyl acetate, washed with water, dried (MgSO4), filtered, and the solvent was evaporated under reduced pressure. The resulting residue was purified by flash chromatography (silica, 0-75% ethyl acetate/hexanes) to afford the title compound as a yellow solid. LRMS (APCI) calc'd for (C20H27N4O5S) [M+H]+, 435.2; found 435.0.

Workup

  1. customThe flask was evacuated
  2. temperatureThe mixture was then cooled
  3. washwashed with water
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent was evaporated under reduced pressure
  7. customThe resulting residue was purified by flash chromatography (silica, 0-75% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-1a16f5ae51f743eeb9fc462ff535fc49
Source dataset
uspto-grants-2012_10
Patent number
US08278335B2

Reaction notes

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