Acetic Acid → HCID 118036450, compound

HRID 1778083Notes

Reaction equation

HRID 1778083 reaction equation
[C:1]([C:3]1[C:4]([N:26]2[CH2:35][CH2:34][C:29]3([CH2:33][NH:32][CH2:31][CH2:30]3)[CH2:28][CH2:27]2)=[CH:5][C:6]([NH:9][C:10]([N:12]2[C:21]3[C:16](=[CH:17][C:18]([CH2:24][OH:25])=[C:19]([CH:22]=[O:23])[N:20]=3)[CH2:15][CH2:14][CH2:13]2)=[O:11])=[N:7][CH:8]=1)#[N:2].C=O.[CH3:38]C(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:1]([C:3]1[C:4]([N:26]2[CH2:27][CH2:28][C:29]3([CH2:33][N:32]([CH3:38])[CH2:31][CH2:30]3)[CH2:34][CH2:35]2)=[CH:5][C:6]([NH:9][C:10]([N:12]2[C:21]3[C:16](=[CH:17][C:18]([CH2:24][OH:25])=[C:19]([CH:22]=[O:23])[N:20]=3)[CH2:15][CH2:14][CH2:13]2)=[O:11])=[N:7][CH:8]=1)#[N:2]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 118036692HCID 118036692, compound2×

Product 1

HCID 118036450HCID 118036450, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of N-(5-cyano-4-(2,8-diazaspiro[4.5]decan-8-yl)pyridin-2-yl)-7-formyl-6-(hydroxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 44, 22 mg, 0.046 mmol) in DCM (0.5 ml) was added formaldehyde (37% in H2O, 0.035 ml, 0.463 mmol) and AcOH (2.65 μl, 0.046 mmol). The reaction mixture was stirred at room temperature for 15 min, then sodium triacetoxyborohydride (14.7 mg, 0.069 mmol) was added and the reaction mixture was stirred for 30 min. The reaction mixture was poured into sat. aq. NaHCO3 and extracted with DCM (2×). The organic phase was then dried over Na2SO4, filtered and evaporated. The crude material was purified by normal phase chromatography (4 g silica gel cartridge, DCM/(DCM/MeOH 9/1+1% Et3N) 100:0 to 0:100) to give the title compound as a colorless powder.

Workup

  1. stirringthe reaction mixture was stirred for 30 min
  2. extractionextracted with DCM (2×)
  3. dry with materialThe organic phase was then dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude material was purified by normal phase chromatography (4 g silica gel cartridge, DCM/(DCM/MeOH 9/1+1% Et3N) 100:0 to 0:100)

Sources & evidence

ORD record
ord-256e0c4c209a4750a1b6f8d2108d8a6c
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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