Methanol → 5-(2-{4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}ethyl)-6-oxo-5,6-dihydro-1,5-naphthyridine-3-carbonitrile Dihydrochloride

HRID 656926Notes

Reaction equation

HRID 656926 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19](=[O:20])[CH:18]=[CH:17][C:16]3[N:15]=[CH:14][C:13]([C:21]#[N:22])=[CH:12][C:11]2=3)[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.CO.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(Cl)(Cl)[Cl:52]>>[ClH:52].[ClH:52].[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](=[O:20])[CH:18]=[CH:17][C:16]5[N:15]=[CH:14][C:13]([C:21]#[N:22])=[CH:12][C:11]4=5)[CH2:6][CH2:7]3)[N:29]=[CH:28][C:27]=2[O:26][CH2:25][CH2:24]1

Participants

6

Reactant 5

HCID 887MethanolHCID 6212ChloroformHCID 5049666Sodium triacetoxyborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 688165971-(2-(4-aminopiperidin-1-yl)ethyl)-7-cyano-1,5-naphthyridin-2(1H)-one

Product 1

HCID 689929795-(2-{4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}ethyl)-6-oxo-5,6-dihydro-1,5-naphthyridine-3-carbonitrile DihydrochlorideYield 92%

Procedure

A solution of 5-[2-(4-amino-1-piperidinyl)ethyl]-6-oxo-5,6-dihydro-1,5-naphthyridine-3-carbonitrile (44 mg, 0.148 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)) (24.5 mg, 0.148 mmol) and 3A molecular sieves in chloroform (1 ml) and MeOH (1 ml) was heated at 65° C. for 5 h, cooled and then NaBH(OAc)3 (63 mg, 0.30 mmol) was added. The reaction was stirred at rt for 18 h, filtered through Celite and evaporated. The residue was treated with sat. aq NaHCO3 solution and a 4:1 DCM:MeOH mixture. The aqueous phase was extracted twice with a 4:1 DCM:MeOH mixture and then the combined organic phases were dried and the solvent was removed under reduced pressure. The residue was subjected to column chromatography on silica gel using a DCM, MeOH and aqueous ammonia gradient to provide the free base of the title compound (0.061 g, 92%).

Workup

  1. temperaturecooled
  2. filtrationfiltered through Celite
  3. customevaporated
  4. additionThe residue was treated with sat. aq NaHCO3 solution
  5. extractionThe aqueous phase was extracted twice with a 4:1 DCM
  6. dry with materialMeOH mixture and then the combined organic phases were dried
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-dfc305e272f24a19a34a05d608616c45
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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