5-(Trifluoromethyl)pyrimidin-2-amine → (S)-2-[4-(5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholine-4-carboxylic acid tert-butyl ester

HRID 2403279ノート

反応式

HRID 2403279 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@@H:10]([C:14]2[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:21][C:22]([F:31])([F:30])[C:23]1[CH:24]=[N:25][C:26]([NH2:29])=[N:27][CH:28]=1>O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@@H:10]([C:14]2[CH:19]=[CH:18][C:17]([NH:29][C:26]3[N:25]=[CH:24][C:23]([C:22]([F:31])([F:21])[F:30])=[CH:28][N:27]=3)=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

4

反応物 2

HCID 152735745-(Trifluoromethyl)pyrimidin-2-amineHCID 58097875tert-butyl (2S)-2-(4-bromophenyl)morpholine-4-carboxylate

生成物 1

HCID 68325411(S)-2-[4-(5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholine-4-carboxylic acid tert-butyl ester収率 108.3%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

To a 10 ml glass vial was added (S)-2-(4-bromo-phenyl)-morpholine-4-carboxylic acid tert-butyl ester (70 mg, CAS 1131220-37-5) and 5-trifluoromethyl-pyrimidin-2-ylamine (66.7 mg, CAS 69034-08-8) in dioxane (2 ml). The reaction mixture was purged with argon for 5 min. 2-Di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (14.3 mg), tris(dibenzylideneacetone)dipalladium(0) (7.49 mg) and sodium tert-butoxide (21.6 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 (S)-2-[4-(5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholine-4-carboxylic acid tert-butyl ester (94 mg, quant.) as an off-white solid. MS (ISP): 425.2 ([M+H]+).

後処理

  1. customThe reaction mixture was purged with argon for 5 min
  2. addition2-Di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (14.3 mg), tris(dibenzylideneacetone)dipalladium(0) (7.49 mg) and sodium tert-butoxide (21.6 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)

出典と根拠

ORDレコード
ord-14c4d712d9e343f581bd3591cd96bc1f
出典データセット
uspto-grants-2014_08
特許番号
US08802673B2

反応ノート

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