Dimethylamine → (R)-N1-(5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-N2,N2-dimethyloxalamide

HRID 64033

反応式

HRID 64033 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:19]=[CH:18][N:17]2[N:20]=[CH:21][C:22]([NH2:23])=[C:16]2[N:15]=1.Cl[C:25](=[O:30])[C:26](OC)=[O:27].C[CH2:32][N:33](C(C)C)[CH:34](C)C.CNC>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:19]=[CH:18][N:17]2[N:20]=[CH:21][C:22]([NH:23][C:25](=[O:30])[C:26]([N:33]([CH3:34])[CH3:32])=[O:27])=[C:16]2[N:15]=1

参加物

6

反応物 4

HCID 674DimethylamineHCID 79846Methyl chloroglyoxylateHCID 81531DiisopropylethylamineHCID 58386314(R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine

生成物 1

HCID 58386298(R)-N1-(5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-N2,N2-dimethyloxalamide収率 73%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a DCM (1 mL) solution of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (Preparation B; 50 mg, 0.16 mmol) was drop-wise added methyl 2-chloro-2-oxoacetate (19.4 mg, 0.159 mmol), followed by DIEA (0.0829 mL, 0.476 mmol). After the mild exothermal subsided and the reaction cooled back to ambient temperature, dimethylamine (0.8 mL, 1.6 mmol) [2M, THF] was added. The reaction was heated to gentle reflux for a few minutes, allowed to cool back to ambient temperature and stirred for 1 hour to reach completion. The reaction was concentrated and directly purified by reverse phase column chromatography, eluting with 5 to 60% acetonitrile/water to yield the final product as a pale-yellowish solid (48 mg, 73% yield). MS (apci) m/z=415.1 (M+H).

後処理

  1. temperatureThe reaction was heated
  2. temperatureto gentle reflux for a few minutes
  3. temperatureto cool back to ambient temperature
  4. concentrationThe reaction was concentrated
  5. customdirectly purified by reverse phase column chromatography
  6. washeluting with 5 to 60% acetonitrile/water

出典と根拠

ORDレコード
ord-d42e2109b1a94fb8a69fff61596accce
出典データセット
uspto-grants-2016_09
特許番号
US09447104B2

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