5-Ethoxypyrimidin-2-amine → HCID 68325477, compound

HRID 2403303Notes

Reaction equation

HRID 2403303 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[CH:19]=[CH:18][C:17](Br)=[C:16]([F:21])[CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:22]([O:24][C:25]1[CH:26]=[N:27][C:28]([NH2:31])=[N:29][CH:30]=1)[CH3:23]>O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[CH:19]=[CH:18][C:17]([NH:31][C:28]3[N:29]=[CH:30][C:25]([O:24][CH2:22][CH3:23])=[CH:26][N:27]=3)=[C:16]([F:21])[CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 450803595-Ethoxypyrimidin-2-amineHCID 68325716Tert-butyl 2-(4-bromo-3-fluorophenyl)morpholine-4-carboxylate

Product 1

HCID 68325477HCID 68325477, compoundYield 18.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a 10 ml glass vial was added (RS)-2-(4-bromo-3-fluoro-phenyl)-morpholine-4-carboxylic acid tert-butyl ester (70 mg, Example 96(e)) and 5-ethoxy-2-pyrimidinamine (40.6 mg, CAS 39268-74-1) in dioxane (2 ml). The reaction mixture was purged with argon for 5 min. 2-Di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (13.6 mg), tris(dibenzylideneacetone)dipalladium(0) (7.12 mg) and sodium tert-butoxide (21.0 mg) were then added. The vial was capped and heated at 120° C. for 16 h. The reaction mixture was then filtered through sintered glass and the filtrate was concentrated in vacuo. The residue was purified by flash column chromatography (silica gel; gradient: 0% to 50% EtOAc in hexanes) to afford (RS)-2-[4-(5-ethoxy-pyrimidin-2-ylamino)-3-fluoro-phenyl]-morpholine-4-carboxylic acid tert-butyl ester (15 mg, 18%) as a yellow gum. MS (ISP): 441.4 ([M+Na]+), 419.3 ([M+H]+).

Workup

  1. customThe reaction mixture was purged with argon for 5 min
  2. addition2-Di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (13.6 mg), tris(dibenzylideneacetone)dipalladium(0) (7.12 mg) and sodium tert-butoxide (21.0 mg) were then added
  3. customThe vial was capped
  4. filtrationThe reaction mixture was then filtered through sintered glass
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe residue was purified by flash column chromatography (silica gel; gradient: 0% to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c9f5a3fecbd14359bc28603ef4e0528f
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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