4-Methylmorpholine → (R)-N-(3-chloropropyl)-5-(2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl)-N-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 1426932ノート

反応式

HRID 1426932 の反応式
[F:1][C:2]1[CH:3]=[C:4]([C@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]2[CH:20]=[CH:19][N:18]3[N:21]=[CH:22][C:23]([C:24](O)=[O:25])=[C:17]3[N:16]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.Cl.[Cl:28][CH2:29][CH2:30][CH2:31][NH:32][CH3:33].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[Cl:28][CH2:29][CH2:30][CH2:31][N:32]([CH3:33])[C:24]([C:23]1[CH:22]=[N:21][N:18]2[CH:19]=[CH:20][C:15]([N:11]3[CH2:12][CH2:13][CH2:14][C@@H:10]3[C:4]3[C:5]([O:8][CH3:9])=[N:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:16][C:17]=12)=[O:25]

参加物

7

反応物 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22107021(3-Chloropropyl)(methyl)amine hydrochlorideHCID 66847769HCID 66847769、化合物

生成物 1

HCID 67470673(R)-N-(3-chloropropyl)-5-(2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl)-N-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide収率 52%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a suspension of (R)-5-(2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (Preparation B, 200 mg, 0.56 mmol) and 3-chloro-N-methylpropan-1-amine hydrochloride (177 mg, 1.23 mmol) in DMF (4 mL) was added N-methylmorpholine (0.25 mL, 2.30 mmol), followed by HATU (234 mg, 0.616 mmol). The reaction was stirred at ambient temperature for 18 hours, then diluted with H2O (10 mL), and extracted EtOAc (2×20 mL). The combined organic extracts were washed with brine (20 mL), dried (MgSO4), filtered, and concentrated. The crude product was purified by reverse-phase column chromatography, eluting with 5 to 60% acetonitrile/water to yield the desired product as a white foamy solid (129 mg, 52% yield). MS (apci) m/z=447.0 (M+H).

後処理

  1. extractionextracted EtOAc (2×20 mL)
  2. washThe combined organic extracts were washed with brine (20 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by reverse-phase column chromatography
  7. washeluting with 5 to 60% acetonitrile/water

出典と根拠

ORDレコード
ord-b7f511ddf06a49d6ae105efc1f97c01a
出典データセット
uspto-grants-2015_01
特許番号
US08933084B2

反応ノート

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