Azetidine → HCID 59472216, compound

HRID 78610Notes

Reaction equation

HRID 78610 reaction equation
CCN(C(C)C)C(C)C.[NH:10]1[CH2:13][CH2:12][CH2:11]1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.[NH2:38][C:39]1[N:40]=[CH:41][C:42]([C:51]2[CH:61]=[CH:60][C:54]([C:55]([N:57]([CH3:59])[CH3:58])=[O:56])=[CH:53][CH:52]=2)=[N:43][C:44]=1[C:45]1[O:46][C:47](=O)[NH:48][N:49]=1>CN(C=O)C>[NH2:38][C:39]1[N:40]=[CH:41][C:42]([C:51]2[CH:52]=[CH:53][C:54]([C:55]([N:57]([CH3:59])[CH3:58])=[O:56])=[CH:60][CH:61]=2)=[N:43][C:44]=1[C:45]1[O:46][C:47]([N:10]2[CH2:13][CH2:12][CH2:11]2)=[N:48][N:49]=1

Participants

6

Reactant 4

HCID 10422AzetidineHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 594716354-(5-amino-6-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-N,N-dimethylbenzamide

Product 1

HCID 59472216HCID 59472216, compoundYield 15.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (38.44 mg, 51.81 μL, 0.2974 mmol), azetidine (8.490 mg, 0.1487 mmol) and bromo(tripyrrolidin-1-yl)phosphonium hexafluorophosphate (76.27 mg, 0.1636 mmol) were added to a solution of 4-(5-amino-6-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-N,N-dimethylbenzamide (50 mg, 0.1487 mmol) in DMF (485.1 μL) and the resulting solution stirred at room temperature for 2 h. The reaction mixture was filtered and purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 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 concentrated in vacuo and triturated with dichloromethane/ diethyl ether to give the product (8.6 mg, 15% yield); 1H NMR (400.0 MHz, DMSO) d 2.96 (s, 3H), 3.00 (s, 6H), 4.25 (t, 4H), 7.52 (dd, 2H), 7.65 (br s, 1H), 8.04-8.06 (m, 2H) and 8.83 (s, 1H) ppm; MS (ES+) 366.21

Workup

  1. filtrationThe reaction mixture was filtered
  2. custompurified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  3. concentrationProduct fractions were concentrated in vacuo
  4. customtriturated with dichloromethane/ diethyl ether

Sources & evidence

ORD record
ord-c0746e294a41484b8d77ed5e93badc56
Source dataset
uspto-grants-2014_09
Patent number
US08841308B2

Reaction notes

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