Sodium triacetoxyborohydride → 1-(2-{4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}ethyl)-5,7-difluoro-2(1H)-quinolinone Diformate

HRID 656939Notes

Reaction equation

HRID 656939 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](=[C:15]([F:21])[CH:16]=[C:17]([F:20])[CH:18]=3)[CH:13]=[CH:12][C:11]2=[O:22])[CH2:4][CH2:3]1.[O:23]1[C:32]2[CH:31]=[C:30]([CH:33]=O)[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1.[BH-](OC(C)=O)(OC(C)=O)[O:36][C:37](C)=[O:38].[Na+]>C(Cl)(Cl)Cl.CO>[CH:37]([OH:38])=[O:36].[CH:37]([OH:38])=[O:36].[O:23]1[C:32]2[CH:31]=[C:30]([CH2:33][NH:1][CH:2]3[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][N:10]4[C:19]5[C:14](=[C:15]([F:21])[CH:16]=[C:17]([F:20])[CH:18]=5)[CH:13]=[CH:12][C:11]4=[O:22])[CH2:6][CH2:7]3)[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1

Participants

6

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 667740021-[2-(4-Amino-1-piperidinyl)ethyl]-5,7-difluoro-2(1H)-quinolinone

Product 1

HCID 866353241-(2-{4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}ethyl)-5,7-difluoro-2(1H)-quinolinone DiformateYield 89%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

1-[2-(4-Amino-1-piperidinyl)ethyl]-5,7-difluoro-2(1H)-quinolinone (150 mg; 0.49 mmol) and 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carboxaldehyde (for a synthesis see WO2004058144, Example 2(c) or WO03/087098, Example 19(d)) (80 mg; 0.49 mmol) were dissolved in a 5:1 mixture of chloroform and MeOH (5 ml: 1 ml) and stirred at rt for 1 h. This was then treated with NaBH(OAc)3 (310 mg; 1.47 mmol) and stirred for a further 2 h under the same conditions. The solvents were then removed from the reaction and the crude residues purified by column chromatography on silica gel using a 0-20% 2M NH3:MeOH/DCM gradient. Fractions containing the desired product were concentrated to afford the free base of the title compound (200 mg; 89%) however this was shown to be impure so was further purified by MDAP to afford the title compound (30 mg; 14%) directly as the diformate salt.

Workup

  1. stirringstirred for a further 2 h under the same conditions
  2. customThe solvents were then removed from the reaction
  3. customthe crude residues purified by column chromatography on silica gel using a 0-20% 2M NH3
  4. additionFractions containing the desired product
  5. concentrationwere concentrated

Sources & evidence

ORD record
ord-5c625aa5162f40179f8928259fb3dcb2
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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