1-Methylpyrrolidine → HCID 71584903, compound

HRID 1257283Notes

Reaction equation

HRID 1257283 reaction equation
[F:1][C:2]1[C:7]([NH:8][C:9]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:10])=[CH:6][C:5]([C:18]2[C:19](=[O:38])[N:20]([CH:35]([CH3:37])[CH3:36])[C:21]3[C:26]([CH:27]=2)=[CH:25][N:24]=[C:23]([NH:28][C:29](=O)[O:30]C(C)=C)[CH:22]=3)=[C:4]([CH3:39])[CH:3]=1.Cl.[NH:41]1[CH2:44][CH2:43][CH2:42]1.CN1CCCC1>O1CCOCC1>[F:1][C:2]1[C:7]([NH:8][C:9]([NH:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[O:10])=[CH:6][C:5]([C:18]2[C:19](=[O:38])[N:20]([CH:35]([CH3:36])[CH3:37])[C:21]3[C:26]([CH:27]=2)=[CH:25][N:24]=[C:23]([NH:28][C:29]([N:41]2[CH2:44][CH2:43][CH2:42]2)=[O:30])[CH:22]=3)=[C:4]([CH3:39])[CH:3]=1

Participants

5

Reactant 3

HCID 84541-MethylpyrrolidineHCID 12308726Azetidine hydrochlorideHCID 86713699HCID 86713699, compound

Product 1

HCID 71584903HCID 71584903, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A suspension of prop-1-en-2-yl (3-(4-fluoro-2-methyl-5-(3-phenylureido)phenyl)-1-isopropyl-2-oxo-1,2-dihydro-1,6-naphthyridin-7-yl)carbamate (0.1 g, 0.189 mmol) in dioxane (3 mL) was treated with azetidine hydrochloride (0.071 g, 0.755 mmol) and 1-methylpyrrolidine (0.129 g, 1.511 mmol) and heated at 70° C. for 16 h, then cooled to RT and stirred for 24 h. The mixture was concentrated to dryness and purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The fractions were neutralized with satd. NaHCO3, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness to afford N-(3-(4-fluoro-2-methyl-5-(3-phenylureido)phenyl)-1-isopropyl-2-oxo-1,2-dihydro-1,6-naphthyridin-7-yl)azetidine-1-carboxamide (43 mg, 43% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.34 (s, 1H), 9.01 (s, 1H), 8.60 (s, 1H), 8.49 (s, 1H), 8.38 (s, 1H), 7.97 (d, J=8.4 Hz, 1H), 7.80 (s, 1H), 7.41 (d, J=8.0 Hz, 2H), 7.25 (t, J=7.8 Hz, 2H), 7.14 (d, J=12.2 Hz, 1H), 6.95 (t, J=7.4 Hz, 1H), 5.35 (m, 1H), 4.02 (t, J=7.5 Hz, 4H), 2.17 (t, J=7.7 Hz, 2H), 2.07 (s, 3H), 1.55 (d, J=7.0 Hz, 6H); MS (ESI) m/z: 529.2 [M+H]+.

Workup

  1. temperaturecooled to RT
  2. concentrationThe mixture was concentrated to dryness
  3. custompurified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA)
  4. extractionNaHCO3, extracted with EtOAc (2×)
  5. washthe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-81d6adbf8688438ba53a8cf9579f1956
Source dataset
uspto-grants-2013_06
Patent number
US08461179B1

Reaction notes

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