Dichloromethane → HCID 44512589, compound

HRID 420694

Reaction equation

HRID 420694 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C@H:9]2[N:19]3[C:20]4[N:11]([C:12](=[O:22])[CH:13]=[CH:14][C:15]=4[CH:16]=[CH:17][C:18]3=[O:21])[CH2:10]2)[CH2:4][CH2:3]1.[F:23][C:24]([F:34])([F:33])[C:25]1[N:30]=[CH:29][C:28]([CH:31]=O)=[CH:27][CH:26]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(Cl)[Cl:50]>CO>[ClH:50].[F:34][C:24]([F:23])([F:33])[C:25]1[N:30]=[CH:29][C:28]([CH2:31][NH:1][CH:2]2[CH2:3][CH2:4][N:5]([CH2:8][C@H:9]3[N:19]4[C:20]5[N:11]([C:12](=[O:22])[CH:13]=[CH:14][C:15]=5[CH:16]=[CH:17][C:18]4=[O:21])[CH2:10]3)[CH2:6][CH2:7]2)=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 27777626-(Trifluoromethyl)pyridine-3-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 58001796HCID 58001796, compound

Product 1

HCID 44512589HCID 44512589, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (1R)-1-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione (see Example 1 step (j) above: 400 mg, 1.33 mmol) and 6-(trifluoromethyl)-3-pyridinecarbaldehyde (233 mg, 1.33 mmol, from Apollo) in a mixture of DCM (5 ml) and MeOH (5 ml) was stirred at room temperature for 2 hour. NaBH(OAc)3 (1.7 g, 7.99 mmol) was then added and the mixture was stirred at room temperature. The reaction was monitored by LCMS. More aldehyde (47 mg, 0.27 mmol), and NaHB(OAc)3 (421 mg, 1.98 mmol) were added and when full conversion was observed, it was quenched with 10% NaHCO3 and extracted with DCM. The organic layer was dried (MgSO4), filtered, and concentrated. Purification by flash chromatography using a 70 g silica gel cartridge, and mixtures of DCM and MeOH as eluent afforded 463 mg (75%) of the expected product as the free base. It was dissolved in MeOH (50 ml). HCl (4M solution in 1,4-dioxane, 0.25 ml, 1 mmol) was added dropwise. After stirring at room temperature for 20 min, the solvent was evaporated. (1R)-1-{[4-({[6-(Trifluoromethyl)-3-pyridinyl]methyl}amino)-1-piperidinyl]methyl}-1,2-dihydro-4H,9H-imidazo[1,2,3-ij]-1,8-naphthyridine-4,9-dione hydrochloride (238 mg, 0.480 mmol, 36%) was obtained as a beige solid.

Workup

  1. stirringthe mixture was stirred at room temperature
  2. customit was quenched with 10% NaHCO3
  3. extractionextracted with DCM
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash chromatography

Sources & evidence

ORD record
ord-73501c436e14499d9a6ea2fd845a3d09
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Linked notes

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