Formaldehyde → HCID 118036629, compound

HRID 1778040Notes

Reaction equation

HRID 1778040 reaction equation
[CH3:1][O:2][CH:3]([O:24][CH3:25])[C:4]1[C:13]([CH2:14][N:15]2[CH2:20][CH2:19][NH:18][C:17]([CH3:22])([CH3:21])[C:16]2=[O:23])=[CH:12][C:11]2[CH2:10][CH2:9][CH2:8][NH:7][C:6]=2[N:5]=1.C=O.[CH2:28](N(CC)CC)C>CO>[CH3:1][O:2][CH:3]([O:24][CH3:25])[C:4]1[C:13]([CH2:14][N:15]2[CH2:20][CH2:19][N:18]([CH3:28])[C:17]([CH3:22])([CH3:21])[C:16]2=[O:23])=[CH:12][C:11]2[CH2:10][CH2:9][CH2:8][NH:7][C:6]=2[N:5]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 8471TriethylamineHCID 118036902HCID 118036902, compound2×

Product 1

HCID 118036629HCID 118036629, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 1-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-3,3-dimethylpiperazin-2-one (intermediate 304, 100 mg, 0.287 mmol), formaldehyde (36.5% in water, 22 μl, 0.290 mmol) and triethylamine (100 μl, 0.721 mmol) in MeOH (2 ml) was stirred at room temperature for 22 days before being partitioned between aqueous saturated NaHCO3 and DCM, extracting 2× with DCM, the combined organic layers dried over Na2SO4 and evaporated. The crude material was preabsorbed onto isolate and purified by normal phase chromatography: 4 g RediSep column, eluting with a gradient from DCM to 95:5 DCM:MeOH containing 1% NH3. The product containing fractions were combined and evaporated to give the title compound as a colourless glass. 1H NMR (400 MHz, CDCl3) δ 7.03 (s, 1H), 5.21 (s, 1H), 4.65 (s, 2H), 3.42-3.35 (m, 8H), 3.20-3.13 (m, 2H), 2.72 (t, 2H), 2.67 (t, 2H), 2.33 (s, 3H), 1.87 (m, 2H), 1.36 (s, 6H).

Workup

  1. custombefore being partitioned between aqueous saturated NaHCO3 and DCM
  2. extractionextracting 2× with DCM
  3. dry with materialthe combined organic layers dried over Na2SO4
  4. customevaporated
  5. customThe crude material was preabsorbed
  6. customonto isolate
  7. custompurified by normal phase chromatography
  8. wash4 g RediSep column, eluting with a gradient from DCM to 95:5 DCM
  9. additionThe product containing fractions
  10. customevaporated

Sources & evidence

ORD record
ord-69c8241c7a0241de84a299600edcd5ec
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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