Ethyl Acetate → HCID 71619629、化合物

HRID 1520240ノート

反応式

HRID 1520240 の反応式
O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[CH2:20]([O:24][C:25]1[N:26]=[CH:27][C:28]([C:31]([OH:33])=O)=[N:29][CH:30]=1)[C:21]#[C:22][CH3:23].[NH2:34][C:35]1[CH:36]=[CH:37][C:38]([F:51])=[C:39]([C@:41]2([CH3:50])[C:46]([F:48])([F:47])[CH2:45][O:44][C:43]([NH2:49])=[N:42]2)[CH:40]=1.C(OCC)(=O)C>CO.C(OC(C)C)(C)C>[NH2:49][C:43]1[O:44][CH2:45][C:46]([F:47])([F:48])[C@:41]([C:39]2[CH:40]=[C:35]([NH:34][C:31]([C:28]3[CH:27]=[N:26][C:25]([O:24][CH2:20][C:21]#[C:22][CH3:23])=[CH:30][N:29]=3)=[O:33])[CH:36]=[CH:37][C:38]=2[F:51])([CH3:50])[N:42]=1

参加物

7

反応物 4

HCID 8857Ethyl AcetateHCID 231494114-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrateHCID 58304207(R)-4-(5-amino-2-fluoro-phenyl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamineHCID 584486775-(But-2-ynyloxy)pyrazine-2-carboxylic acid

生成物 1

HCID 71619629HCID 71619629、化合物収率 63.2%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒2 回HCID 7914Diisopropyl Ether溶媒

反応条件

温度
0 °C

実験手順

A solution of 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (DMTMM) (74 mg, 0.25 mmol) in methanol (5 ml) was cooled to 0° C. and treated with 5-(but-2-ynyloxy)pyrazine-2-carboxylic acid (CAS[1221447-98-8]) (40.8 mg, 0.21 mmol). The suspension was stirred at 0° C. for 30 minutes, then a solution of (R)-4-(5-amino-2-fluoro-phenyl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (intermediate A8.1) (50 mg, 0.19 mmol) in methanol (1 ml) was added dropwise. The resulting yellow solution was stirred at 0° C. for 4 hours. For the workup, the reaction mixture was evaporated at reduced pressure and the residue treated with a saturated solution of sodium carbonate (10 ml). Extraction with ethyl acetate, combination of the organic layers, drying over sodium sulphate, and evaporation at reduced pressure yielded the crude product. After chromatography on a silica-NH2 phase using ethyl acetate as the eluent, the product was obtained as a yellowish oil which, after trituration in isopropyl ether, yielded the 5-but-2-ynyloxy-pyrazine-2-carboxylic acid [3-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-4-fluoro-phenyl]-amide (52 mg, 63% yield) as a white solid. MS (ISP): m/z=434.2 [M+H]+.

後処理

  1. stirringThe resulting yellow solution was stirred at 0° C. for 4 hours
  2. customFor the workup, the reaction mixture was evaporated at reduced pressure
  3. additionthe residue treated with a saturated solution of sodium carbonate (10 ml)
  4. extractionExtraction with ethyl acetate, combination of the organic layers
  5. dry with materialdrying over sodium sulphate, and evaporation at reduced pressure
  6. customyielded the crude product
  7. customthe product was obtained as a yellowish oil which

出典と根拠

ORDレコード
ord-0305045e0a784150bae7c24a3c040d18
出典データセット
uspto-grants-2015_07
特許番号
US09073909B2

反応ノート

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