Cesium carbonate → (R)-tert-butyl 3-((5-(2-(1H-pyrrol-1-yl)thiazol-4-yl)-6-methoxy-2-morpholinopyrimidin-4-yl)amino)piperidine-1-carboxylate

HRID 1507494Notes

Reaction equation

HRID 1507494 reaction equation
I[C:2]1[C:3]([NH:16][CH:17]2[CH2:22][CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18]2)=[N:4][C:5]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[N:6][C:7]=1[O:8][CH3:9].[N:30]1([C:35]2[S:36][CH:37]=[C:38](B3OC(C)(C)C(C)(C)O3)[N:39]=2)[CH:34]=[CH:33][CH:32]=[CH:31]1.C([O-])([O-])=O.[Cs+].[Cs+]>[Pd+2].Cl[Cu].CN(C=O)C>[N:30]1([C:35]2[S:36][CH:37]=[C:38]([C:2]3[C:3]([NH:16][C@@H:17]4[CH2:22][CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:28])([CH3:29])[CH3:27])=[O:24])[CH2:18]4)=[N:4][C:5]([N:10]4[CH2:11][CH2:12][O:13][CH2:14][CH2:15]4)=[N:6][C:7]=3[O:8][CH3:9])[N:39]=2)[CH:34]=[CH:33][CH:32]=[CH:31]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 457859762-(1H-pyrrol-1-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazoleHCID 117677619Tert-butyl 3-((5-iodo-6-methoxy-2-morpholinopyrimidin-4-yl)amino)piperidine-1-carboxylate

Product 1

HCID 117677378(R)-tert-butyl 3-((5-(2-(1H-pyrrol-1-yl)thiazol-4-yl)-6-methoxy-2-morpholinopyrimidin-4-yl)amino)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 105144Allyl(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)chloropalladium(II)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

In a 40 mL vial chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl)]-palladium(II) (0.023 g, 0.029 mmol), tert-butyl 3-((5-iodo-6-methoxy-2-morpholinopyrimidin-4-yl)amino)piperidine-1-carboxylate (Compound (21) (0.15 g, 0.289 mmol), 2-(1H-pyrrol-1-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole (0.088 g, 0.318 mmol) and CuCl (0.031 g, 0.318 mmol) were combined. This mixture was then evacuated and backfilled with argon. Then DMF (2.89 ml) and Cs2CO3 (0.376 g, 1.16 mmol) were added to this flask all under argon. This mixture was then heated at 100° C. for 18 h. The mixture was cooled, filtered, diluted with ethyl acetate (mL), washed with water, then dried (Na2SO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified via column chromatography. (0-50% EtOAc/hexane) to give the title compound as a white solid. MS (m/z)=542 (M+H).

Workup

  1. customThis mixture was then evacuated
  2. temperatureThe mixture was cooled
  3. filtrationfiltered
  4. additiondiluted with ethyl acetate (mL)
  5. washwashed with water
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified via column chromatography

Sources & evidence

ORD record
ord-edfc0df8dce94c6fa712bd82958981d8
Source dataset
uspto-grants-2015_12
Patent number
US09221809B2

Reaction notes

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