Dimethylformamide dimethyl acetal → (3Z)-1-Cyclopropyl-4-(dimethylamino)-3-[2-(pyridin-4-ylamino)pyrimidin-4-yl]but-3-en-2-one

HRID 2359749Notes

Reaction equation

HRID 2359749 reaction equation
[CH:1]1([CH2:4][C:5](=[O:20])[CH2:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[N:8]=2)[CH2:3][CH2:2]1.[CH3:21][N:22]([CH:24](OC)OC)[CH3:23]>>[CH:1]1([CH2:4][C:5](=[O:20])/[C:6](/[C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[N:8]=2)=[CH:21]\[N:22]([CH3:24])[CH3:23])[CH2:2][CH2:3]1

Participants

3

Reactant 2

HCID 78373Dimethylformamide dimethyl acetalHCID 679838261-Cyclopropyl-3-[2-(pyridin-4-ylamino)pyrimidin-4-yl]propan-2-one

Product 1

HCID 67983720(3Z)-1-Cyclopropyl-4-(dimethylamino)-3-[2-(pyridin-4-ylamino)pyrimidin-4-yl]but-3-en-2-oneYield 99%

Conditions

Temperature
80 °C

Procedure

1-Cyclopropyl-3-[2-(pyridin-4-ylamino)pyrimidin-4-yl]propan-2-one (8) (269 mg, 1.003 mmol) was taken up in DMF-DMA (5.369 mL, 40.1 mmol) and stirred at 80° C. for 30 minutes. The solvent was evaporated and the residue partitioned between DCM and water. The organic layer was washed with saturated sodium bicarbonate and brine, dried with sodium sulfate, and concentrated in vacuo. The crude residue was purified by Biotage™ silica gel chromatography [1-13% MeOH in DCM with 1% triethylamine] to afford the desired product as an orange/brown foam (320 mg, 99% yield). MS (ES+): m/z=324.3 (100) [MH+2]. HPLC: tR=0.88 minute over 3 minutes. Purity: >90% [HPLC (LC/MS) at 220 nm].

Workup

  1. customThe solvent was evaporated
  2. customthe residue partitioned between DCM and water
  3. washThe organic layer was washed with saturated sodium bicarbonate and brine
  4. dry with materialdried with sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified by Biotage™ silica gel chromatography [1-13% MeOH in DCM with 1% triethylamine]

Sources & evidence

ORD record
ord-b1da0ff4d63d4d7891fc539870f84d26
Source dataset
uspto-grants-2014_04
Patent number
US08685993B2

Reaction notes

Loading…