Dimethylformamide → HCID 118071210, compound

HRID 920813Notes

Reaction equation

HRID 920813 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10](C(O)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[Cl:32][C:33]1[CH:34]=[C:35]([C:40]2[C:48]([C:49]([NH2:51])=[O:50])=[C:43]3[CH2:44][NH:45][CH2:46][CH2:47][N:42]3[N:41]=2)[CH:36]=[CH:37][C:38]=1[F:39].C[N:53]([CH:55]=[O:56])C>C1(C)C=CC=CC=1>[C:49]([C:48]1[C:40]([C:35]2[CH:36]=[CH:37][C:38]([F:39])=[C:33]([Cl:32])[CH:34]=2)=[N:41][N:42]2[CH2:47][CH2:46][N:45]([C:55]([NH:53][CH:10]3[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:11]3)=[O:56])[CH2:44][C:43]=12)(=[O:50])[NH2:51]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 199401P,P-Diphenylphosphinic azideHCID 27559811-Boc-Azetidine-3-carboxylic acidHCID 1180616272-(3-Chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxamide

Product 1

HCID 118071210HCID 118071210, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of Intermediate 1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid (273 mg, 1.47 mmol) in toluene (6 mL) was added TEA (0.472 ml, 3.39 mmol) followed by DPPA (0.22 ml, 1.0 mmol) and the mixture was stirred at 90° C. for 1 h. The reaction mixture was cooled to RT and a solution of Intermediate 185B (200 mg, 0.679 mmol) in DMF (2 mL) was added and stirring continued at RT for 16 h. The reaction was quenched with a 10% aq. solution of NaHCO3, the organic layer was separated, dried over sodium sulfate, and concentrated. The crude product was purified by silica gel chromatography (4 g REDISEP® column, eluting with 5% MeOH in CHCl3). Fractions containing the product were combined and evaporated to afford Intermediate 339A as a buff colored solid (250 mg, 75% yield) MS(ES): m/z=493.

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. stirringstirring
  3. waitcontinued at RT for 16 h
  4. customThe reaction was quenched with a 10% aq. solution of NaHCO3
  5. customthe organic layer was separated
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe crude product was purified by silica gel chromatography (4 g REDISEP® column, eluting with 5% MeOH in CHCl3)
  9. additionFractions containing the product
  10. customevaporated

Sources & evidence

ORD record
ord-95871df38f32449e8e8e61a482b027fd
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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