Sodium Carbonate → HCID 71283456, compound

HRID 1752443Notes

Reaction equation

HRID 1752443 reaction equation
[C:1]([CH:4]1[CH2:9][N:8]([CH3:10])[CH2:7][CH2:6][N:5]1[C:11]1[N:16]=[C:15](Cl)[N:14]=[C:13]([C:18]([NH2:20])=[O:19])[CH:12]=1)(=[O:3])[NH2:2].CC1(C)C(C)(C)OB([C:29]2[CH:34]=[CH:33][C:32]([O:35][C:36]3[CH:41]=[CH:40][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:38][CH:37]=3)=[CH:31][CH:30]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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]>[C:1]([CH:4]1[CH2:9][N:8]([CH3:10])[CH2:7][CH2:6][N:5]1[C:11]1[N:16]=[C:15]([C:29]2[CH:30]=[CH:31][C:32]([O:35][C:36]3[CH:41]=[CH:40][C:39]([C:42]([F:43])([F:44])[F:45])=[CH:38][CH:37]=3)=[CH:33][CH:34]=2)[N:14]=[C:13]([C:18]([NH2:20])=[O:19])[CH:12]=1)(=[O:3])[NH2:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 66806437HCID 66806437, compoundHCID 89422629HCID 89422629, compound

Product 1

HCID 71283456HCID 71283456, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 6-(2-carbamoyl-4-methylpiperazin-1-yl)-2-chloropyrimidine-4-carboxamide (0.300 g, 1.00 mmol) in dioxane (5 mL) was added 4,4,5,5-tetramethyl-2-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,3,2-dioxaborolane (0.404 g, 1.11 mmol), 2M aqueous Na2CO3 (1.0 mL, 2.0 mmol) and PdCl2(dppf) (0.046 g, 0.056 mmol). The reaction vessel was flushed with argon, sealed and heated at 100° C. overnight. After cooling, the reaction mixture was evaporated in vacuo and the residue chromatographed over silica gel with 0-20% MeOH in acetone. The product fractions were evaporated in vacuo and the residue triturated with 1:1 acetonitrile/MeOH (5 mL). The solid was filtered, washed with MeOH (1×1 mL), and acetonitrile (1×1 mL). An additional batch of material was obtained by evaporation of the filtrates, trituration of the residue with 1:1 acetonitrile/MeOH (2 mL) and washing the solid with MeOH (1×0.5 mL) then acetonitrile (1×0.5 mL). The combined solids were dried under vacuum at 40° C. to give 6-(2-carbamoyl-4-methylpiperazin-1-yl)-2-(4-(4-(trifluoromethyl)phenoxy)phenyl)pyrimidine-4-carboxamide as a very pale tan powder (0.271 g, 0.541 mmol, 54% yield). 1H NMR (400 MHz, CD3OD): 8.57 (2H, d, J=9.0 Hz), 7.71 (2H, d, J=8.6 Hz), 7.39 (1H, s), 7.21 (2H, d, J=8.6 Hz), 7.16 (2H, d, J=9.0 Hz), 5.68-5.23 (1H, br), 4.49-3.93 (1H, br), 3.65-3.54 (1H, m), 3.51-3.43 (1H, m), 3.00-2.93 (1H, m), 2.40 (1H, dd, J=12.1 Hz, 4.6 Hz), 2.34 (3H, s), 2.21 (1H, dt, J=11.8 Hz, 3.5 Hz). LC/MS: m/z=501.1 [M+H]+.

Workup

  1. customThe reaction vessel was flushed with argon
  2. customsealed
  3. temperatureAfter cooling
  4. customthe reaction mixture was evaporated in vacuo
  5. customthe residue chromatographed over silica gel with 0-20% MeOH in acetone
  6. customThe product fractions were evaporated in vacuo
  7. customthe residue triturated with 1:1 acetonitrile/MeOH (5 mL)
  8. filtrationThe solid was filtered
  9. washwashed with MeOH (1×1 mL), and acetonitrile (1×1 mL)
  10. customAn additional batch of material was obtained by evaporation of the filtrates, trituration of the residue with 1:1 acetonitrile/MeOH (2 mL)
  11. washwashing the solid with MeOH (1×0.5 mL)
  12. customThe combined solids were dried under vacuum at 40° C.

Sources & evidence

ORD record
ord-b3ea7a96b89e4f25a09083f2ef5c2247
Source dataset
uspto-grants-2015_10
Patent number
US09163008B2

Reaction notes

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