1,4-Dioxane → 1-(3,3-Dimethylcyclobutyl)-3-(2-fluoro-5-(2-((2-methoxyethyl)amino)-7-methylpyrido[2,3-d]pyrimidin-6-yl)-4-methylphenyl)urea

HRID 522741Notes

Reaction equation

HRID 522741 reaction equation
[NH2:1][C:2]1[C:3]([F:25])=[CH:4][C:5]([CH3:24])=[C:6]([C:8]2[C:22]([CH3:23])=[N:21][C:11]3[N:12]=[C:13]([NH:16][CH2:17][CH2:18][O:19][CH3:20])[N:14]=[CH:15][C:10]=3[CH:9]=2)[CH:7]=1.[CH3:26][C:27]1([CH3:34])[CH2:30][CH:29](C(O)=O)[CH2:28]1.C1C=CC(P([N:49]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[O:52]1[CH2:57]COCC1>>[CH3:34][C:27]1([CH3:26])[CH2:28][CH:29]([NH:49][C:57]([NH:1][C:2]2[CH:7]=[C:6]([C:8]3[C:22]([CH3:23])=[N:21][C:11]4[N:12]=[C:13]([NH:16][CH2:17][CH2:18][O:19][CH3:20])[N:14]=[CH:15][C:10]=4[CH:9]=3)[C:5]([CH3:24])=[CH:4][C:3]=2[F:25])=[O:52])[CH2:30]1

Participants

5

Reactant 4

HCID 312751,4-DioxaneHCID 199401P,P-Diphenylphosphinic azideHCID 2151063,3-Dimethylcyclobutanecarboxylic acidHCID 898134956-(5-Amino-4-fluoro-2-methylphenyl)-N-(2-methoxyethyl)-7-methylpyrido[2,3-d]pyrimidin-2-amine

Product 1

HCID 898141381-(3,3-Dimethylcyclobutyl)-3-(2-fluoro-5-(2-((2-methoxyethyl)amino)-7-methylpyrido[2,3-d]pyrimidin-6-yl)-4-methylphenyl)ureaYield 13%

Procedure

Treat a solution of 6-(5-amino-4-fluoro-2-methylphenyl)-N-(2-methoxyethyl)-7-methylpyrido[2,3-d]pyrimidin-2-amine (0.270 g, 0.791 mmol) in dioxane (5 mL) with 3,3-dimethylcyclobutane carboxylic acid (0.122 g, 0.949 mmol) followed by DPPA (0.261 g, 0.949 mmol) and TEA (0.160 g, 1.582 mmol), stir at RT for 20 minutes, heat to 90° C. for 2 h and then cool to RT overnight. Concentrate the mixture to dryness, purify via silica gel chromatography (20-100% EtOAc/Hexanes) and triturate with MeCN. Collect the resulting material via filtration and re-purify via silica gel chromatography (20-100% EtOAc/Hexanes) to afford the title compound as a yellow solid (55 mg, 13% yield). MS (m/z): 467.3 (M+1).

Workup

  1. temperatureheat to 90° C. for 2 h
  2. temperaturecool to RT overnight
  3. concentrationConcentrate the mixture to dryness
  4. custompurify via silica gel chromatography (20-100% EtOAc/Hexanes)
  5. customtriturate with MeCN
  6. customCollect the resulting material
  7. filtrationvia filtration
  8. customre-purify via silica gel chromatography (20-100% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-845ad886205a445794e9c6a363de62d1
Source dataset
uspto-grants-2016_05
Patent number
US09334267B2

Reaction notes

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