Cyclopropylamine → HCID 89606168, compound

HRID 1430433Notes

Reaction equation

HRID 1430433 reaction equation
[NH2:1][C:2]1[C:3]([F:23])=[CH:4][C:5]([CH3:22])=[C:6]([C:8]2[C:9](=[O:21])[N:10]([CH2:19][CH3:20])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13](Cl)[CH:12]=3)[CH:7]=1.[CH:24]1([NH2:27])[CH2:26][CH2:25]1>CCO.CN(C1C=CN=CC=1)C>[NH2:1][C:2]1[C:3]([F:23])=[CH:4][C:5]([CH3:22])=[C:6]([C:8]2[C:9](=[O:21])[N:10]([CH2:19][CH3:20])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([NH:27][CH:24]2[CH2:26][CH2:25]2)[CH:12]=3)[CH:7]=1

Participants

5

Reactant 2

HCID 69828Cyclopropylamine2×HCID 87666922HCID 87666922, compound

Product 1

HCID 89606168HCID 89606168, compoundYield 23.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

A solution of Example A6 (500 mg, 1.507 mmol) and cyclopropylamine (860 mg, 15.07 mmol) in EtOH (15 mL) was heated at 100° C. in a sealed vessel. After 20 h the reaction mixture was treated with additional cyclopropylamine (860 mg, 15.07 mmol) and catalytic DMAP (10 mg) and heated at 100° C. for 23 h, then 115° C. for 10 days. The mixture was cooled to RT, concentrated to dryness and the resulting residue dissolved in EtOAc (30 mL) and washed successively with water (30 mL), satd. NaHCO3 (30 mL) and brine (30 mL). The organic phase was dried over Na2SO4, concentrated to dryness and purified by reverse phase chromatography (MeCN/H2O with 0.1% TFA). The aqueous solution was treated with satd. NaHCO3 (5 mL) and allowed to stand. A solid formed which was collected by filtration to yield 3-(5-amino-4-fluoro-2-methylphenyl)-7-(cyclopropylamino)-1-ethyl-1,6-naphthyridin-2(1H)-one (124 mg, 23% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.36 (s, 1H), 7.60 (s, 1H), 7.28 (s, 1H), 6.83 (d, 1H), 6.58 (d, 1H), 6.38 (s, 1H), 4.87 (s, 2H), 4.18-4.12 (m, 2H), 2.59 (m, 1H), 1.94 (s, 3H), 1.21 (t, 3H), 0.75 (m, 2H), 0.47 (m, 2H); MS (ES-API) m/z: 353.1 [M+H]+.

Workup

  1. temperatureThe mixture was cooled to RT
  2. concentrationconcentrated to dryness
  3. dissolutionthe resulting residue dissolved in EtOAc (30 mL)
  4. washwashed successively with water (30 mL)
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. custompurified by reverse phase chromatography (MeCN/H2O with 0.1% TFA)
  8. additionThe aqueous solution was treated with satd
  9. customA solid formed which
  10. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-27ba4bf4b8bb453bb0f68fa1e444d79a
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

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