Methyl Acrylate → (E)-methyl 3-(4-(1-acetyl-5-cyclopropyl-1H-pyrazol-3-ylamino)-2-phenylpyrimidin-5-yl)acrylate

HRID 1484865Notes

Reaction equation

HRID 1484865 reaction equation
[CH:1]1([C:4]2[N:8]([C:9](=[O:11])[CH3:10])[N:7]=[C:6]([NH:12][C:13]3[C:18](I)=[CH:17][N:16]=[C:15]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[N:14]=3)[CH:5]=2)[CH2:3][CH2:2]1.[C:26]([O:30][CH3:31])(=[O:29])[CH:27]=[CH2:28].N(C)(C1CCCCC1)C1CCCCC1.P(C(C)(C)C)(C(C)(C)C)C(C)(C)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:9]([N:8]1[C:4]([CH:1]2[CH2:3][CH2:2]2)=[CH:5][C:6]([NH:12][C:13]2[C:18](/[CH:28]=[CH:27]/[C:26]([O:30][CH3:31])=[O:29])=[CH:17][N:16]=[C:15]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:14]=2)=[N:7]1)(=[O:11])[CH3:10]

Participants

7

Reactant 4

HCID 7294Methyl AcrylateHCID 24210N-Methyl dicyclohexylamineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 581693201-(5-cyclopropyl-3-(5-iodo-2-phenylpyrimidin-4-ylamino)-1H-pyrazol-1-yl)ethanone

Product 1

HCID 66927424(E)-methyl 3-(4-(1-acetyl-5-cyclopropyl-1H-pyrazol-3-ylamino)-2-phenylpyrimidin-5-yl)acrylateYield 7.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1-(5-cyclopropyl-3-(5-iodo-2-phenylpyrimidin-4-ylamino)-1H-pyrazol-1-yl)ethanone (3 g, 6.72 mmol, 1.0 equiv.), methyl acrylate (2.28 g, 26.8 mmol, 4.0 equiv.), Pd2(dba)3 (600 mg, 0.6 mmol, 0.1 equiv.), Cy2NMe (1.35 g, 7.2 mmol, 1.1 equiv.) and P(t-Bu)3 (540 mg, 2.4 mmol, 0.4 equiv.) in dioxane (100 mL) was heated to 120° C. for 3 h under nitrogen atmosphere. Then, the reaction mixture was cooled to room temperature and filtered. The residue was crystallized with methane/diisopropyl ether to afford (E)-methyl 3-(4-(1-acetyl-5-cyclopropyl-1H-pyrazol-3-ylamino)-2-phenylpyrimidin-5-yl)acrylate (200 mg, 7.3%). LC-MS (m/z): 404.1 [M+H]+. 1H NMR: (400 MHz, DMSO-d6) δ 0.83-0.84 (m, 2H), 1.03-1.04 (m, 2H), 2.04 (m, 1H), 2.64 (s, 3H), 3.77 (s, 3H), 6.83 (d, J=16.0 Hz, 1H), 6.84 (s, 1H), 7.57-7.58 (m, 3H), 7.71 (d, J=16.0 Hz, 1H), 8.34 (m, 2H), 8.97 (s, 1H), 10.74 (s, 1H).

Workup

  1. temperatureThen, the reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. customThe residue was crystallized with methane/diisopropyl ether

Sources & evidence

ORD record
ord-9dddea0cfb604561808ba18d7a482ab8
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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