Acryloyl chloride → N-(3-{[2-({1-[2-(dimethylamino)ethyl]-1H-pyrazol-4-yl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy}phenyl)prop-2-enamide

HRID 577671Notes

Reaction equation

HRID 577671 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][CH:28]=1)[O:5][C:6]1[C:7]2[CH:25]=[CH:24][NH:23][C:8]=2[N:9]=[C:10]([NH:12][C:13]2[CH:14]=[N:15][N:16]([CH2:18][CH2:19][N:20]([CH3:22])[CH3:21])[CH:17]=2)[N:11]=1.[C:29](Cl)(=[O:32])[CH:30]=[CH2:31]>C1COCC1>[CH3:21][N:20]([CH3:22])[CH2:19][CH2:18][N:16]1[CH:17]=[C:13]([NH:12][C:10]2[N:11]=[C:6]([O:5][C:4]3[CH:3]=[C:2]([NH:1][C:29](=[O:32])[CH:30]=[CH2:31])[CH:28]=[CH:27][CH:26]=3)[C:7]3[CH:25]=[CH:24][NH:23][C:8]=3[N:9]=2)[CH:14]=[N:15]1

Participants

4

Reactant 2

HCID 13140Acryloyl chlorideHCID 866796154-(3-aminophenoxy)-N-{1-[2-(dimethylamino)ethyl]-1H-pyrazol-4-yl}-7H-pyrrolo[2,3-d]pyrimidin-2-amine

Product 1

HCID 86679616N-(3-{[2-({1-[2-(dimethylamino)ethyl]-1H-pyrazol-4-yl}amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy}phenyl)prop-2-enamideYield 11%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

To a solution of 4-(3-aminophenoxy)-N-{1-[2-(dimethylamino)ethyl]-1H-pyrazol-4-yl}-7H-pyrrolo[2,3-d]pyrimidin-2-amine in THF (5 mL) which was cooled to 10° C. was added prop-2-enoyl chloride (47.8 mg, 0.528 mmol) and stirred at 10° C. for 3 hrs. The volatiles were removed in vacuo and the residue purified by HPLC (Phenominex Gemini C18, 21.2×100 mm, 5 μm column using the water/acetonitrile with 10 mM ammonium acetate, with the flow rate 40 mL/min with gradient 55%-67% acetonitrile in 6 min) which was then lyophilized to afford the title compound (28.5 mg, 11% yield) as a tan solid. 1H NMR (600 MHz, DMSO-D6) δ ppm 11.06-11.23 (m, 1H) 9.96-10.08 (m, 1H) 8.56-8.64 (m, 1H) 7.56-7.66 (m, 2H) 7.39-7.47 (m, 2H) 7.30-7.36 (m, 1H) 6.94-7.02 (m, 2H) 6.37-6.47 (m, 1H) 6.18-6.30 (m, 2H) 5.68-5.80 (m, 1H) 3.89-4.04 (m, 2H) 2.57-2.64 (m, 2H) 2.18 (s, 6H). m/z (ESI+) for C22H24N8O2 433.2 (M+H)+.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue purified by HPLC (Phenominex Gemini C18, 21.2×100 mm, 5 μm column
  3. waitwith the flow rate 40 mL/min with gradient 55%-67% acetonitrile in 6 min) which was then lyophilized

Sources & evidence

ORD record
ord-62ba727d6b04423eb2978beddbc7465d
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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