tert-Butanol → 4-[5-amino-6-[5-[4-(1,2-dihydroxyethyl)phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-N,N-dimethyl-benzamide

HRID 2204864ノート

反応式

HRID 2204864 の反応式
CC[C@H]1[C@H]2C[C@H]([C@H](OC3C4C(=CC=CC=4)C(O[C@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C([O:22]C)C=C4)N(CC2)C1.CS(N)(=O)=O.[NH2:64][C:65]1[N:66]=[CH:67][C:68]([C:84]2[CH:94]=[CH:93][C:87]([C:88]([N:90]([CH3:92])[CH3:91])=[O:89])=[CH:86][CH:85]=2)=[N:69][C:70]=1[C:71]1[O:72][C:73]([C:76]2[CH:81]=[CH:80]C(C=C)=[CH:78][CH:77]=2)=[N:74][N:75]=1.[O-]S([O-])(=S)=O.[Na+].[Na+].[Na+].[Cl-].[C:104]([OH:108])(C)([CH3:106])[CH3:105]>O>[NH2:64][C:65]1[N:66]=[CH:67][C:68]([C:84]2[CH:94]=[CH:93][C:87]([C:88]([N:90]([CH3:92])[CH3:91])=[O:89])=[CH:86][CH:85]=2)=[N:69][C:70]=1[C:71]1[O:72][C:73]([C:76]2[CH:81]=[CH:80][C:105]([CH:104]([OH:108])[CH2:106][OH:22])=[CH:78][CH:77]=2)=[N:74][N:75]=1

参加物

7

反応物 5

HCID 6386tert-ButanolHCID 72879MethanesulfonamideHCID 510036741-((1R)-((2R,4R,5S)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)-4-((1R)-((2R,4S,5R)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)phthalazineHCID 594723394-[5-amino-6-[5-(4-vinylphenyl)-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-N,N-dimethyl-benzamideHCID 86645023Na2S2O3 NaCl

生成物 1

HCID 594717644-[5-amino-6-[5-[4-(1,2-dihydroxyethyl)phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-N,N-dimethyl-benzamide収率 36%

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

AD-mix-Alpha (450 mg) and methanesulfonamide (20.53 mg, 0.2158 mmol) in a mixture of t-butanol (2 mL)/water (2 mL) were stirred at room temperature until dissolved, then cooled to 0° C. and treated with 4-[5-amino-6-[5-(4-vinylphenyl)-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-N,N-dimethyl-benzamide (89 mg, 0.2158 mmol). The reaction mixture was stirred vigorously and warmed to room temperature overnight. A further portion of AD-mix (300 g) was added and the reaction mixture stirred overnight at room temperature to give complete conversion. The reaction mixture was treated with Na2S2O3/NaCl solution and extracted into ethyl acetate (10 mL), dried over MgSO4 and concentrated under reduced pressure to give a yellow solid. This was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. Product fractions were combined and lypholised to give the product as a pale yellow powder (28.4 mg, 36% yield); 1H NMR (400 MHz, DMSO) d 2.9-3.02 (m, 6H), 3.51 (m, 2H), 4.67 (m, 1H), 4.83 (m, 1H), 5.49 (m, 1H), 7.55 (d, 2H), 7.64 (d, 2H), 7.78 (br s, 2H), 8.11 (d, 2H), 8.18 (d, 2H) and 8.98 (s, 1H) ppm; MS (ES+) 447.25

後処理

  1. dissolutionuntil dissolved
  2. temperaturecooled to 0° C.
  3. stirringThe reaction mixture was stirred vigorously
  4. temperaturewarmed to room temperature overnight
  5. additionA further portion of AD-mix (300 g) was added
  6. stirringthe reaction mixture stirred overnight at room temperature
  7. customto give complete conversion
  8. extractionextracted into ethyl acetate (10 mL)
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated under reduced pressure
  11. customto give a yellow solid
  12. customThis was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]

出典と根拠

ORDレコード
ord-31491f29974b478eb657bbdd59e3d7ee
出典データセット
uspto-grants-2016_06
特許番号
US09365557B2

反応ノート

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