N,N-Dimethylethylenediamine → HCID 69296282, compound

HRID 1930454Notes

Reaction equation

HRID 1930454 reaction equation
[CH:1]1([C:6]2[CH:10]=[C:9]([NH:11][C:12]([NH:14][C:15]3[CH:20]=[C:19]([C:21]4[C:32](=[O:33])[N:31]([CH3:34])[C:24]5[N:25]=[C:26]([NH:29][CH3:30])[N:27]=[CH:28][C:23]=5[CH:22]=4)[C:18]([CH3:35])=[CH:17][C:16]=3[F:36])=[O:13])[N:8]([CH3:37])[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:38][N:39]([CH3:43])[CH2:40]CN>C1COCC1.CCOC(C)=O>[CH:1]1([C:6]2[CH:10]=[C:9]([NH:11][C:12]([NH:14][C:15]3[CH:20]=[C:19]([C:21]4[C:32](=[O:33])[N:31]([CH3:34])[C:24]5[N:25]=[C:26]([NH:29][CH2:30][CH2:38][N:39]([CH3:43])[CH3:40])[N:27]=[CH:28][C:23]=5[CH:22]=4)[C:18]([CH3:35])=[CH:17][C:16]=3[F:36])=[O:13])[N:8]([CH3:37])[N:7]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 2

HCID 66053N,N-DimethylethylenediamineHCID 69297520HCID 69297520, compound

Product 1

HCID 69296282HCID 69296282, compoundYield 39.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution 1-(3-cyclopentyl-1-methyl-1H-pyrazol-5-yl)-3-(2-fluoro-4-methyl-5-(8-methyl-2-(methylsulfinyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl)phenyl)urea from Example 122 (80 mg, 0.15 mmol) in THF (1 mL) was treated with N,N-dimethylethylenediamine (0.080 mL, 0.74 mmol). The reaction was stirred 1 h at RT, diluted with EtOAc (15 mL) and washed with 2 M aq Na2CO3 (2×10 mL), water (10 mL) and brine (10 mL). The organics were dried (Na2SO4), concentrated in vacuo and chromatographed on reverse phase silica gel to provide 1-(3-cyclopentyl-1-methyl-1H-pyrazol-5-yl)-3-(5-(2-(2-(dimethylamino)ethylamino)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl)-2-fluoro-4-methylphenyl)urea (33 mg, 39% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.87 (s, 1H), 8.72 (d, J=2.0 Hz, 1H), 8.65 and 8.60 (br s, 1H), 7.91 (d, J=8.6 Hz, 1H), 7.75 and 7.59 (m, 1H), 7.66 (s, 1H), 7.14 (d, J=8.4 Hz, 1H), 5.98 (s, 1H), 3.59-3.43 (m, 8H), 2.86 (m, 1H), 2.21 (br s, 6H), 2.49 (m, 2H obscured by solvent), 2.06 (s, 3H), 1.87 (m, 2H), 1.66-1.48 (m, 6H); MS (ESI) m/z: 562.3 (M+H+).

Workup

  1. washwashed with 2 M aq Na2CO3 (2×10 mL), water (10 mL) and brine (10 mL)
  2. dry with materialThe organics were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customchromatographed on reverse phase silica gel

Sources & evidence

ORD record
ord-07fa6a18031c4db5884d64916e05b538
Source dataset
uspto-grants-2012_05
Patent number
US08188113B2

Reaction notes

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