5-(Trifluoromethyl)pyrimidin-2-amine → HCID 68325424, compound

HRID 2403312Notes

Reaction equation

HRID 2403312 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].[F:22][C:23]([F:32])([F:31])[C:24]1[CH:25]=[N:26][C:27]([NH2:30])=[N:28][CH:29]=1>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:30][C:27]3[N:26]=[CH:25][C:24]([C:23]([F:32])([F:22])[F:31])=[CH:29][N:28]=3)=[C:16]([F:21])[CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 152735745-(Trifluoromethyl)pyrimidin-2-amineHCID 68325716Tert-butyl 2-(4-bromo-3-fluorophenyl)morpholine-4-carboxylate

Product 1

HCID 68325424HCID 68325424, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a 20 ml glass vial was added (RS)-2-(4-bromo-3-fluoro-phenyl)-morpholine-4-carboxylic acid tert-butyl ester (200 mg, example 96(e)) and 5-trifluoromethyl-pyrimidin-2-ylamine (145 mg, CAS 69034-08-8) in dioxane (5 ml). The reaction mixture was purged with argon for 5 min. 2-Di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (38.9 mg), tris(dibenzylideneacetone)dipalladium(0) (20.3 mg) and sodium tert-butoxide (59.9 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 heptane) to afford (RS)-2-[3-fluoro-4-(5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholine-4-carboxylic acid tert-butyl ester (115 mg, 47%) as a yellow gum. MS (ISP): 441.4 ([M−H]−).

Workup

  1. customThe reaction mixture was purged with argon for 5 min
  2. addition2-Di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (38.9 mg), tris(dibenzylideneacetone)dipalladium(0) (20.3 mg) and sodium tert-butoxide (59.9 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 heptane)

Sources & evidence

ORD record
ord-3ff9c4e8f5ed464080cd59098f050393
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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