Sodium triacetoxyborohydride → 2-Oxo-1-[2-(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)methyl]amino)piperidin-1-yl)ethyl]-1,2-dihydroquinoxaline-6-carbonitrile

HRID 255361Notes

Reaction equation

HRID 255361 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[CH:15][C:16]([C:20]#[N:21])=[CH:17][CH:18]=3)[N:13]=[CH:12][C:11]2=[O:22])[CH2:4][CH2:3]1.[O:23]=[C:24]1[CH2:29][O:28][C:27]2[CH:30]=[CH:31][C:32]([CH:34]=O)=[N:33][C:26]=2[NH:25]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[O:22]=[C:11]1[CH:12]=[N:13][C:14]2[C:19](=[CH:18][CH:17]=[C:16]([C:20]#[N:21])[CH:15]=2)[N:10]1[CH2:9][CH2:8][N:5]1[CH2:6][CH2:7][CH:2]([NH:1][CH2:34][C:32]2[CH:31]=[CH:30][C:27]3[O:28][CH2:29][C:24](=[O:23])[NH:25][C:26]=3[N:33]=2)[CH2:3][CH2:4]1

Participants

4

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 218737373-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehydeHCID 667741351-[2-(4-Aminopiperidin-1-yl)ethyl]-2-oxo-1,2-dihydroquinoxaline-6-carbonitrile2×

Product 1

HCID 667745582-Oxo-1-[2-(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)methyl]amino)piperidin-1-yl)ethyl]-1,2-dihydroquinoxaline-6-carbonitrileYield 65.7%

Procedure

1-[2-(4-Aminopiperidin-1-yl)ethyl]-2-oxo-1,2-dihydroquinoxaline-6-carbonitrile (Intermediate 197, 0.125 g) was reacted with 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehyde (WO 2004/058144) (0.17 g) and NaBH(OAc)3 (0.27 g) as described for Example 107. The residue was purified by reverse phase HPLC with acetonitrile in water containing 0.1% TFA. Fractions containing product were concentrated to remove acetonitrile, neutralized with Na2CO3 solid, extracted with ethyl acetate, dried (Na2SO4), filtered and concentrated. The residue was suspended in diethyl ether and filtered to yield 127 mg of a colorless solid.

Workup

  1. customThe residue was purified by reverse phase HPLC with acetonitrile in water containing 0.1% TFA
  2. additionFractions containing product
  3. concentrationwere concentrated
  4. customto remove acetonitrile
  5. extractionextracted with ethyl acetate
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. filtrationfiltered

Sources & evidence

ORD record
ord-06f9effabb244d728f8d68ad0df2c869
Source dataset
uspto-grants-2011_01
Patent number
US07875715B2

Reaction notes

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