Pyrrolidine → HCID 59487110, compound

HRID 2195720Notes

Reaction equation

HRID 2195720 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:20]=[C:19]([N+:21]([O-:23])=[O:22])[CH:18]=[CH:17][C:16]=3[CH3:24])[N:9]=2)[CH:5]=[N:6][CH:7]=1.[NH:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CS(C)=O.[Cu]I>[CH3:24][C:16]1[CH:17]=[CH:18][C:19]([N+:21]([O-:23])=[O:22])=[CH:20][C:15]=1[NH:14][C:10]1[N:9]=[C:8]([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([N:25]3[CH2:29][CH2:28][CH2:27][CH2:26]3)[CH:3]=2)[CH:13]=[CH:12][N:11]=1

Participants

6

Reactant 3

HCID 31268PyrrolidineHCID 62657Potassium Phosphate, TribasicHCID 23073501HCID 23073501, compound

Product 1

HCID 59487110HCID 59487110, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
160 °C

Procedure

(2-Meth yl-5-nitro-phenyl)-[4-(5-pyrrolidin-1-yl-pyridin-3-yl)-pyrimidin-2-yl]-amine 9 is prepared by mixing 8 (0.40 g, 1.04 mmol), pyrrolidine (3.12 mmol), K3PO4 (0.44 g, 2.08 mmol), CuI (38.5 mg, 0.10 mmol) and L-proline amino acid (48.1 mg, 0.21 mmol) in DMSO (8 ml) and heating at 160° C. in a microwave oven for 20 min. The cooled mixture is partitioned between water and ethyl acetate. The organic layer is separated, and the aqueous layer is extracted with ethyl acetate. The combined organic layers are washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue is dissolved in DMSO (4 mL) and purified with HPLC to afford pure product 9. 1H NMR (400 MHz, d-CDCl3) δ 9.23 (d, J=2.4 Hz, 1H), 8.63 (d, J=5.2 Hz, 1H), 8.58 (s, 1H), 8.10 (s, 1H), 8.04 (s, 1H), 7.90 (dd, J=8.4, 2.4 Hz, 1H), 7.44 (s, 1H), 7.39 (d, J=8.4 Hz, 1H), 7.30 (d, J=5.2 Hz, 1H), 3.43-3.48 (m, 4H), 2.49 (s, 3H), 2.12-2.16 (m, 4H). LC/MS (m/z) (M+1)+: 377.2.

Workup

  1. custom(2-Meth yl-5-nitro-phenyl)-[4-(5-pyrrolidin-1-yl-pyridin-3-yl)-pyrimidin-2-yl]-amine 9 is prepared
  2. customThe cooled mixture is partitioned between water and ethyl acetate
  3. customThe organic layer is separated
  4. extractionthe aqueous layer is extracted with ethyl acetate
  5. washThe combined organic layers are washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue is dissolved in DMSO (4 mL)
  9. custompurified with HPLC

Sources & evidence

ORD record
ord-94a99a083d29467ead53249260538696
Source dataset
uspto-grants-2012_12
Patent number
US08338417B2

Reaction notes

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