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 78643Notes

Reaction equation

HRID 78643 reaction equation
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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

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

Workup

  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]

Sources & evidence

ORD record
ord-a3525718a2ca4197b0051afe7ef2fd8c
Source dataset
uspto-grants-2014_09
Patent number
US08841308B2

Reaction notes

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