Potassium Carbonate → Thiazolo[4,5-c]pyridine-6-carboxylic acid,2-[(1-methylethyl)amino]-,methyl ester

HRID 1452967Notes

Reaction equation

HRID 1452967 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[N:8]=[C:9]([NH:11][CH:12]([CH3:14])[CH3:13])[S:10][C:4]=2[CH:3]=1.[C:15]1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:44]([O-:47])([O-])=[O:45].[K+].[K+]>CO.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:12]([NH:11][C:9]1[S:10][C:4]2[CH:3]=[C:2]([C:44]([O:47][CH3:15])=[O:45])[N:7]=[CH:6][C:5]=2[N:8]=1)([CH3:14])[CH3:13]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 575272276-chloro-N-isopropylthiazolo[4,5-c]pyridin-2-amine

Product 1

HCID 57527243Thiazolo[4,5-c]pyridine-6-carboxylic acid,2-[(1-methylethyl)amino]-,methyl esterYield 301.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 6-chloro-N-isopropylthiazolo[4,5-c]pyridin-2-amine (0.24 g, 1.05 mmol, 1.0 eq.), Pd(OAc)2 (0.0313 g, 0.139 mmol, 0.1 eq.), 1,3-bis(diphenylphosphino)propane (0.0443 g, 0.107 mmol, 0.1 eq.) and K2CO3 (0.2214 g, 1.60 mmol, 1.5 eq.) in MeOH (2.6 mL) and DMF (1.3 mL) was stirred under an atmosphere of CO inside a bomb (40 psi) at 91° C. overnight. After cooling to room temperature, the reaction mixture was filtered through Celite and rinsed with MeOH. The filtrate was concentrated in vacuo, diluted with EtOAc and water. The layers were separated, and the organic layer was washed with brine and 10% aqueous LiCl, dried over Na2SO4, filtered and concentrated in vacuo. The residue was triturated with CH2Cl2:MeOH (10:0.3) to give methyl 2-(isopropylamino)thiazolo[4,5-c]pyridine-6-carboxylate as a white solid (0.081 g, 31% yield).

Workup

  1. filtrationthe reaction mixture was filtered through Celite
  2. washrinsed with MeOH
  3. concentrationThe filtrate was concentrated in vacuo
  4. additiondiluted with EtOAc and water
  5. customThe layers were separated
  6. washthe organic layer was washed with brine and 10% aqueous LiCl
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was triturated with CH2Cl2:MeOH (10:0.3)

Sources & evidence

ORD record
ord-b4d6cabc7d6349d6af2901154b2e17e2
Source dataset
uspto-grants-2009_01
Patent number
US07473784B2

Reaction notes

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