Diisopropylethylamine → (S)-tert-Butyl 2-(4-(2,5-dichloropyrimidin-4-ylamino)phenyl)morpholine-4-carboxylate

HRID 2403325Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[CH:4][CH:3]=1.[Cl:21][C:22]1[N:27]=[C:26](Cl)[C:25]([Cl:29])=[CH:24][N:23]=1.C(N(C(C)C)CC)(C)C>CC(O)C>[Cl:21][C:22]1[N:27]=[C:26]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([C@@H:8]3[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]3)=[CH:4][CH:3]=2)[C:25]([Cl:29])=[CH:24][N:23]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of (5)-tert-butyl 2-(4-aminophenyl)morpholine-4-carboxylate (100 mg, 0.36 mmol), 2,4,5-trichloropyrimidine (66 mg, 0.36 mmol) and diisopropylethylamine (70 mg, 0.54 mmol) was dissolved in 2-propanol (1.5 ml) and stirred at 80° C. overnight. For work-up most of the solvent was evaporated, then aqueous ammonium chloride solution was added and the mixture was extracted with ethyl acetate. The aqueous phase was re-extracted with ethyl acetate twice. The combined organic layers were dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography (20 g silica gel, 10 to 30% ethyl acetate in heptane) to yield a white solid (141 mg, 92%). MS (ISP): 425.1 ([{35Cl}M+H]+), 427.1 ([{37Cl}M+H]+).

Workup

customFor work-up most of the solvent was evaporated
additionaqueous ammonium chloride solution was added
extractionthe mixture was extracted with ethyl acetate
extractionThe aqueous phase was re-extracted with ethyl acetate twice
dry with materialThe combined organic layers were dried (MgSO4)
concentrationconcentrated in vacuo
customThe residue was purified by flash chromatography (20 g silica gel, 10 to 30% ethyl acetate in heptane)

Sources & evidence

ORD record: ord-cb55a6e6cfa5407b90cabf107984ed2d
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08802673B2

Reaction notes

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