1-(2-Chloro-3,6-difluorobenzyl)-7-(6-morpholin-4-yl-pyridin-3-yl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine → 3,6-Difluoro-2-[7-(6-morpholin-4-yl-pyridin-3-yl)-3,4-dihydro-2H-pyrido[2,3-b]pyrazin-1-ylmethyl]benzonitrile

HRID 2074693Notes

Reaction equation

HRID 2074693 reaction equation
Cl[C:2]1[C:30]([F:31])=[CH:29][CH:28]=[C:27]([F:32])[C:3]=1[CH2:4][N:5]1[CH2:10][CH2:9][NH:8][C:7]2[N:11]=[CH:12][C:13]([C:15]3[CH:16]=[N:17][C:18]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)=[CH:19][CH:20]=3)=[CH:14][C:6]1=2.[C:33]([Cu])#[N:34]>CN(C=O)C>[F:32][C:27]1[C:3]([CH2:4][N:5]2[CH2:10][CH2:9][NH:8][C:7]3[N:11]=[CH:12][C:13]([C:15]4[CH:16]=[N:17][C:18]([N:21]5[CH2:22][CH2:23][O:24][CH2:25][CH2:26]5)=[CH:19][CH:20]=4)=[CH:14][C:6]2=3)=[C:2]([C:30]([F:31])=[CH:29][CH:28]=1)[C:33]#[N:34]

Participants

4

Reactant 2

HCID 578861351-(2-Chloro-3,6-difluorobenzyl)-7-(6-morpholin-4-yl-pyridin-3-yl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazineHCID 178418546HCID 178418546, compound

Product 1

HCID 578860773,6-Difluoro-2-[7-(6-morpholin-4-yl-pyridin-3-yl)-3,4-dihydro-2H-pyrido[2,3-b]pyrazin-1-ylmethyl]benzonitrileYield 37%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

1-(2-Chloro-3,6-difluorobenzyl)-7-(6-morpholin-4-yl-pyridin-3-yl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazine (300 mg) was dissolved in anhydrous DMF. CuCN (5.0 eq) was added and the resulting mixture was heated to 150° C. in a microwave for 30 minutes. The reaction mixture was concentrated, taken up in CH2Cl2, washed three (3) times with an aqueous solution of NH4OH (10%), and the organic phase was dried, filtered, and concentrated. The residue was purified via silica gel chromatography (0-100% ethyl acetate in hexanes followed by 5% methanol in ethyl acetate) to give the title compound (37% yield). M.p 188-190° C., LCMS: m/z=449.05 (M+H+), 1H-NMR (CDCl3, 400 MHz) δ 3.24-3.31 (m, 2H), 3.48-3.56 (m, 6H), 3.80-3.88 (m, 4H), 4.51 (s, 2H), 4.86 (bs, 1H), 6.65-6.73 (m, 1H), 6.98-7.06 (m, 2H), 7.09-7.19 (m, 2H), 7.59-7.64 (m, 2H), 8.36 (s, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. washwashed three (3) times with an aqueous solution of NH4OH (10%)
  3. customthe organic phase was dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified via silica gel chromatography (0-100% ethyl acetate in hexanes followed by 5% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-8591620fa2164b04b0e379b647f37941
Source dataset
uspto-grants-2011_04
Patent number
US07919502B2

Reaction notes

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