Sodium Bicarbonate → 1-(2-{4-[(2,3-Dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one 5-oxide Hydrochloride

HRID 657084Notes

Reaction equation

HRID 657084 reaction equation
[ClH:1].Cl.[NH2:3][CH:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][N:12]2[C:21]3[CH:20]=[C:19]([F:22])[CH:18]=[N+:17]([O-:23])[C:16]=3[CH:15]=[CH:14][C:13]2=[O:24])[CH2:6][CH2:5]1.[O:25]1[C:30]2=[CH:31][N:32]=[C:33]([CH:35]=O)[CH:34]=[C:29]2C[CH2:27][CH2:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=[O:39])C.[Na+].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.C(Cl)Cl.C(N(CC)CC)C.CO>[ClH:1].[O:39]1[C:29]2[CH:34]=[C:33]([CH2:35][NH:3][CH:4]3[CH2:5][CH2:6][N:7]([CH2:10][CH2:11][N:12]4[C:21]5[CH:20]=[C:19]([F:22])[CH:18]=[N+:17]([O-:23])[C:16]=5[CH:15]=[CH:14][C:13]4=[O:24])[CH2:8][CH2:9]3)[N:32]=[CH:31][C:30]=2[O:25][CH2:26][CH2:27]1

Participants

9

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 566403113,4-dihydro-2H-pyrano[2,3-c]pyridine-6-carbaldehydeHCID 688201601-[2-(4-Amino-1-piperidinyl)ethyl]-7-fluoro-1,5-naphthyridin-2(1H)-one 5-oxide Dihydrochloride

Product 1

HCID 689927451-(2-{4-[(2,3-Dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one 5-oxide Hydrochloride

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

1-[2-(4-Amino-1-piperidinyl)ethyl]-7-fluoro-1,5-naphthyridin-2(1H)-one 5-oxide dihydrochloride (100 mg, 0.264 mmol) was stirred in chloroform (2 mL) plus methanol (0.1 mL), and triethylamine (0.130 mL) was added. After stirring for 10 minutes at room temperature 3,4-dihydro-2H-pyrano[2,3-c]pyridine-6-carbaldehyde (for a synthesis see WO2004058144, Example 126(e)) (44 mg, 1 eq.) was added and the mixture was stirred at rt for a further 3 hours before addition of sodium triacetoxyborohydride (168 mg, 3 eq.). After a further 3 hours, saturated aqueous sodium hydrogen cabonate (1 ml) was added and the organic phase was diluted with DCM to bring the total volume to ca. 50 ml. The organic phase was separated using a hydrophobic frit and the aqueous phase was extracted with DCM (2×20 ml). The combined DCM extracts were evaporated under reduced pressure and purified by MDAP to give the free base of the title compound as a tan amorphous solid (39 mg).

Workup

  1. additionwas added
  2. customThe organic phase was separated
  3. extractionthe aqueous phase was extracted with DCM (2×20 ml)
  4. customThe combined DCM extracts were evaporated under reduced pressure
  5. custompurified by MDAP

Sources & evidence

ORD record
ord-02bd0a6f09ba4d6a88e72219a0979411
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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