Acryloyl chloride → HCID 86732022, compound

HRID 527409Notes

Reaction equation

HRID 527409 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9]1[CH:10]=[C:11]([N:15]2[C:20]3[N:21]=[C:22]([NH:25][C:26]4[CH:31]=[CH:30][C:29]([N:32]5[CH2:37][CH2:36][O:35][CH2:34][CH2:33]5)=[CH:28][C:27]=4[O:38][CH3:39])[N:23]=[CH:24][C:19]=3[CH:18]=[CH:17][C:16]2=[O:40])[CH:12]=[CH:13][CH:14]=1.CCN(C(C)C)C(C)C.[C:50](Cl)(=[O:53])[CH:51]=[CH2:52].C([O-])(O)=O.[Na+]>O.C(Cl)Cl>[CH3:39][O:38][C:27]1[CH:28]=[C:29]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[CH:30]=[CH:31][C:26]=1[NH:25][C:22]1[N:23]=[CH:24][C:19]2[CH:18]=[CH:17][C:16](=[O:40])[N:15]([C:11]3[CH:10]=[C:9]([NH:8][C:50](=[O:53])[CH:51]=[CH2:52])[CH:14]=[CH:13][CH:12]=3)[C:20]=2[N:21]=1

Participants

7

Reactant 4

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 86732018HCID 86732018, compound

Product 1

HCID 86732022HCID 86732022, compoundYield 49.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

8-(3-Aminophenyl)-2-((2-methoxy-4-morpholinophenyl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one 2,2,2-trifluoroacetate (2b, 63 mg, 0.11 mmol) was treated with DCM (5.0 mL), cooled to 0° C. and treated with DIEA (0.06 mL, 0.34 mmol) and acryloyl chloride (9.16 μL, 0.113 mmol) and stirred at 0° C. for 40 min. The reaction mixture was treated with ice and water and then a saturated solution of NaHCO3. It was extracted with DCM (3×25 mL), dried over Na2SO4, filtered and concentrated. The crude residue was purified on a Gilson prepatory HPLC (Silicycle Silichrome XT C18 column; 30×150 mm, 5μ, 20-95% 0.1% TFA/CH3CN in 0.1% TFA/water) affording N-(3-(2-((2-methoxy-4-morpholinophenyl)amino)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide (2) (26 mg, 0.054 mmol, 47% yield) as a light orange amorphous solid after concentration of the sample containing fractions, treatment with a saturated solution of NaHCO3, extraction with DCM (3×25 mL), drying over Na2SO4, filtration and drying under vacuum. m/z (ESI, +ve ion) 500.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.33 (1H, s), 8.88 (1H, s), 8.04 (1H, d, J=9.6 Hz), 7.66-7.70 (1H, m), 7.64 (1H, d, J=8.2 Hz), 7.45 (1H, t, J=8.0 Hz), 6.94-7.00 (1H, m), 6.90 (1H, d, J=8.6 Hz), 6.67 (1H, d, J=9.6 Hz), 6.59 (1H, d, J=2.5 Hz), 6.42-6.51 (1H, m), 6.40 (1H, dd, J=8.8, 2.5 Hz), 6.22-6.32 (1H, m), 5.77-5.82 (1H, m), 3.71-3.80 (4H, m), 3.63 (3H, s), 3.04-3.14 (4H, m).

Workup

  1. extractionIt was extracted with DCM (3×25 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified on a Gilson prepatory HPLC (Silicycle Silichrome XT C18 column; 30×150 mm, 5μ, 20-95% 0.1% TFA/CH3CN in 0.1% TFA/water)

Sources & evidence

ORD record
ord-fc16e03bf5754172b059ebdaf2e93b50
Source dataset
uspto-grants-2016_05
Patent number
US09346801B2

Reaction notes

Loading…