Potassium Carbonate → HCID 46202640, compound

HRID 72806Notes

Reaction equation

HRID 72806 reaction equation
C(OC([N:8]1[CH2:14][CH2:13][C:12]2[C:15](OS(C(F)(F)F)(=O)=O)=[N:16][C:17]([N:19]3[CH2:24][CH2:23][S:22](=[O:26])(=[O:25])[CH2:21][CH2:20]3)=[N:18][C:11]=2[CH2:10][CH2:9]1)=O)(C)(C)C.[CH3:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1.C([O-])([O-])=O.[K+].[K+]>CC(=O)C.C1(C)C=CC=CC=1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[O:25]=[S:22]1(=[O:26])[CH2:21][CH2:20][N:19]([C:17]2[N:16]=[C:15]([C:39]3[CH:40]=[CH:41][C:36]([CH3:35])=[CH:37][CH:38]=3)[C:12]3[CH2:13][CH2:14][NH:8][CH2:9][CH2:10][C:11]=3[N:18]=2)[CH2:24][CH2:23]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 79799Tolylboronic acidHCID 866570822-(1,1-Dioxo-1lambda6-thiomorpholin-4-yl)-4 trifluoromethanesulfonyloxy-5,6,8,9-tetrahydro-pyrimido[4,5-d]azepine-7-carboxylic acid tert-butyl ester

Product 1

HCID 46202640HCID 46202640, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 866570832-Propanone toluene waterSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2-(1,1-dioxo-1λ6-thiomorpholin-4-yl)-4 trifluoromethanesulfonyloxy-5,6,8,9-tetrahydro-pyrimido[4,5-d]azepine-7-carboxylic acid tert-butyl ester (0.0008 mol), (4-methylphenyl)-boronic acid (0.0008 mol), Pd(dppf)Cl2 (0.00008 mol) and K2CO3 (0.0016 mol) in 2-propanone/toluene/water (4:4:1, 8 mL) was stirred in a microwave for 30 min at 130° C. The separated organic layer was filtered over silica gel and the filtrate was concentrated. The residue was purified by FCC (petroleum ether/Et2O). The product fractions were collected and the solvent was evaporated. This residue was dissolved in TFA/DCM/water (5:12:1, 12 mL) and stirred at rt for 90 min. The mixture was concentrated and residue was diluted with 1 M NaOH and extracted with DCM (2×). The combined organic layers were washed with satd. NaCl, dried, and concentrated. The residue was recrystallized from 2-propanol to give 0.190 g (64%) of the title compound.

Workup

  1. filtrationThe separated organic layer was filtered over silica gel
  2. concentrationthe filtrate was concentrated
  3. customThe residue was purified by FCC (petroleum ether/Et2O)
  4. customThe product fractions were collected
  5. customthe solvent was evaporated
  6. dissolutionThis residue was dissolved in TFA/DCM/water (5:12:1, 12 mL)
  7. stirringstirred at rt for 90 min
  8. concentrationThe mixture was concentrated
  9. additionresidue was diluted with 1 M NaOH
  10. extractionextracted with DCM (2×)
  11. washThe combined organic layers were washed with satd
  12. dry with materialNaCl, dried
  13. concentrationconcentrated
  14. customThe residue was recrystallized from 2-propanol

Sources & evidence

ORD record
ord-f5e3b4d898c04fed87046d3ce1e0178b
Source dataset
uspto-grants-2014_09
Patent number
US08829011B2

Reaction notes

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