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 1644491Notes

Reaction equation

HRID 1644491 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-d7898e55c36141a39482080ff0332efd
Source dataset
uspto-grants-2012_02
Patent number
US08124602B2

Reaction notes

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