Ethyl Acetate → HCID 71619629, 화합물

HRID 1520240

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HRID 1520240 반응식
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

참가 물질

7

반응물 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

생성물 1

HCID 71619629HCID 71619629, 화합물수율 63.2%

시약·촉매·용매 2

HCID 887Methanol용매2회HCID 7914Diisopropyl Ether용매

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온도
0 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-0305045e0a784150bae7c24a3c040d18
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073909B2

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