Nitrogen → HCID 90258498, compound

HRID 1051203Notes

Reaction equation

HRID 1051203 reaction equation
[CH3:1][C:2]([CH3:12])([CH3:11])[C:3]([NH:5][C:6]1[CH:10]=[CH:9][NH:8][N:7]=1)=[O:4].Cl[CH2:14][C@@H:15]1[CH2:19][O:18][C:17]([CH3:21])([CH3:20])[O:16]1.CC(C)([O-])C.[Na+].N#N>CN(C=O)C>[CH3:20][C:17]1([CH3:21])[O:16][C@H:15]([CH2:14][N:8]2[CH:9]=[CH:10][C:6]([NH:5][C:3](=[O:4])[C:2]([CH3:12])([CH3:11])[CH3:1])=[N:7]2)[CH2:19][O:18]1

Participants

6

Reactant 4

HCID 947NitrogenHCID 6930483(S)-4-Chloromethyl-2,2-dimethyl-1,3-dioxolaneHCID 23676156Sodium t-butoxide2×HCID 178447232HCID 178447232, compound4×

Product 1

HCID 90258498HCID 90258498, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

2,2-Dimethyl-N-(1H-pyrazol-3-yl)-propionamide (1.67 g, 10 mmol) was dissolved in DMF (17 ml). (S)-4-Chloromethyl-2,2-dimethyl-[1,3]dioxolane (1.52 g, 10 mmol) was added into the mixture. Finally Sodium tert-butoxide (0.98 g, 10 mmol) was added at room temperature. The mixture was heated to 100° C. with agitation for 23 hours under N2 atmosphere. UPLC indicated that there was 26% 2,2-Dimethyl-N-(1H-pyrazol-3-yl)-propionamide remained in the mixture. Additional 2,2-Dimethyl-N-(1H-pyrazol-3-yl)-propionamide (0.76 g, 5 mmol) and Sodium tert-butoxide (0.49 g, 5 mmol) was added. The mixture was stirred at 100° C. for another 24 hrs. HPLC indicated 2,2-Dimethyl-N-(1H-pyrazol-3-yl)-propionamide was 9.4% remained, the selectivity of N1/N2 alkylation products was 2.8:1. The DMF was concentrated under reduced pressure. Water (10 ml) was added. The mixture was extracted with DCM (2×12 ml), the organic layer was washed with 10% aqueous NaCl (2×20 ml). The organic layer was dried over Na2SO4, concentrated under reduced pressure to give oil, which is purified by silicon column (hexane/EA=5:1 to hexane/EA=3:1) to give off-white solid (0.84 g), yield: 30%. 1H-NMR (400 MHz, d6-DMSO): δ 9.85 (s, 1H), 7.59 (s, 1H), 6.47 (s, 1H), 4.36-4.39 (m, 1H), 4.08-4.12 (m, 2H), 4.0-4.02 (m, 1H), 3.73-3.75 (m, 1H), 1.33 (s, 3H), 1.26 (s, 3H), 1.19 (s, 9H).

Workup

  1. concentrationThe DMF was concentrated under reduced pressure
  2. additionWater (10 ml) was added
  3. extractionThe mixture was extracted with DCM (2×12 ml)
  4. washthe organic layer was washed with 10% aqueous NaCl (2×20 ml)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto give oil, which
  8. customis purified by silicon column (hexane/EA=5:1 to hexane/EA=3:1)

Sources & evidence

ORD record
ord-db7effdcc98e4924b2c4f70a5178af09
Source dataset
uspto-grants-2016_07
Patent number
US09388168B2

Reaction notes

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