Difluoroacetic acid → (R)-1-(2-((7-chloropyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholino)-2,2-difluoroethanone

HRID 57594

反応式

HRID 57594 の反応式
[Cl:1][C:2]1[N:11]=[C:10]([NH:12][CH2:13][C@H:14]2[O:19][CH2:18][CH2:17][N:16]([C:20]([O:22]C(C)(C)C)=O)[CH2:15]2)[C:9]2[C:4](=[N:5][CH:6]=[CH:7][N:8]=2)[CH:3]=1.[F:27][CH:28]([F:32])C(O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>Cl.C(OCC)(=O)C>[Cl:1][C:2]1[N:11]=[C:10]([NH:12][CH2:13][C@@H:14]2[CH2:15][N:16]([C:20](=[O:22])[CH:28]([F:32])[F:27])[CH2:17][CH2:18][O:19]2)[C:9]2[C:4](=[N:5][CH:6]=[CH:7][N:8]=2)[CH:3]=1

参加物

7

反応物 4

HCID 9788Difluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86706988(R)-tert-butyl 2-((7-chloropyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholine-4-carboxylate

生成物 1

HCID 86717395(R)-1-(2-((7-chloropyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholino)-2,2-difluoroethanone収率 73.4%

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid溶媒HCID 8857Ethyl Acetate溶媒

実験手順

The (R)-tert-butyl 2-((7-chloropyrido[4,3-b]pyrazin-5-ylamino)methyl)morpholine-4-carboxylate (3.00 g, 8.0 mmol) was dissolved in the solution of HCl in ethyl acetate (20 mL), and the mixture was stirred at room temperature for 2 hours until TLC indicated Boc group was removed. The volatile materials were removed in vacuo and the residues were dissolved in dichloromethane. To the solution, difluoroacetic acid (1.15 g, 12 mmol), HATU (7.60 g, 20.0 mmol) and DIPEA (6.20 g, 48.0 mmol) were added subsequently and stirred at room temperature overnight. The mixture was purified by C18 column chromatography to give the desired amide as yellow solid (2.1 g). MS (m/z): 358 (M+H)+

後処理

  1. customwas removed
  2. customThe volatile materials were removed in vacuo
  3. dissolutionthe residues were dissolved in dichloromethane
  4. stirringstirred at room temperature overnight
  5. customThe mixture was purified by C18 column chromatography

出典と根拠

ORDレコード
ord-af6f85c86d074fb0b57f5217055f1022
出典データセット
uspto-grants-2016_09
特許番号
US09434726B2

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