Methanol → N-(2-(2-(4-(4-acetylpiperazin-1-yl)-2-methoxyphenylamino)-5-chloropyrimidin-4-yloxy)phenyl) acrylamide

HRID 2284908Notes

Reaction equation

HRID 2284908 reaction equation
[NH2:1][C:2]1[CH:33]=[CH:32][CH:31]=[CH:30][C:3]=1[O:4][C:5]1[C:10]([Cl:11])=[CH:9][N:8]=[C:7]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][N:22]([C:25](=[O:27])[CH3:26])[CH2:21][CH2:20]3)=[CH:15][C:14]=2[O:28][CH3:29])[N:6]=1.CCN(C(C)C)C(C)C.[C:43](Cl)(=[O:46])[CH:44]=[CH2:45].CO>C(Cl)Cl.C(Cl)(Cl)Cl>[C:25]([N:22]1[CH2:23][CH2:24][N:19]([C:16]2[CH:17]=[CH:18][C:13]([NH:12][C:7]3[N:6]=[C:5]([O:4][C:3]4[CH:30]=[CH:31][CH:32]=[CH:33][C:2]=4[NH:1][C:43](=[O:46])[CH:44]=[CH2:45])[C:10]([Cl:11])=[CH:9][N:8]=3)=[C:14]([O:28][CH3:29])[CH:15]=2)[CH2:20][CH2:21]1)(=[O:27])[CH3:26]

Participants

7

Reactant 4

HCID 887MethanolHCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 867296351-(4-(4-(4-(2-Aminophenoxy)-5-chloropyrimidin-2-ylamino)-3-methoxy phenyl)piperazin-1-yl)ethanone

Product 1

HCID 86729636N-(2-(2-(4-(4-acetylpiperazin-1-yl)-2-methoxyphenylamino)-5-chloropyrimidin-4-yloxy)phenyl) acrylamide

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 1-(4-(4-(4-(2-aminophenoxy)-5-chloropyrimidin-2-ylamino)-3-methoxy phenyl)piperazin-1-yl)ethanone (75 mg, 0.16 mmol) in DCM (5 mL), DIPEA (42 mg, 0.33 mmol) and acryloyl chloride (15 mg, 0.165 mmol) were added at −78° C., and the mixture was stirred for 15 min. TLC showed completion of starting material (TLC system: 10% methanol in chloroform (Rf): 0.2). The reaction mixture was quenched with water (15 mL) and extracted with DCM (2×10 mL). The organic layer was separated, dried over sodium sulphate, and concentrated. Crude compound was purified by prep-HPLC to obtain N-(2-(2-(4-(4-acetylpiperazin-1-yl)-2-methoxyphenylamino)-5-chloropyrimidin-4-yloxy)phenyl) acrylamide as a yellow solid. (Yield: 28 mg, 33.7%). MS: m/z 523.2 (ES+, M+H). 1HNMR (DMSO-d6) δ 9.54 (s, 1H), 8.33 (s, 1H), 8.01 (s, 1H), 7.99 (br s, 1H), 7.25 (m, 4H), 6.56 (s, 1H), 6.50 (d, 1H, J=10.4 Hz), 6.22 (br s, 1H), 6.127 (s, 1H), 5.70 (dd, 1H, J=2.0, 10.4 Hz), 3.73 (s, 3H), 3.57 (m, 4H), 3.06 (br t, 2), 3.00 (br t, 2H), 2.03 (s, 3H).

Workup

  1. customThe reaction mixture was quenched with water (15 mL)
  2. extractionextracted with DCM (2×10 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated
  6. customCrude compound was purified by prep-HPLC

Sources & evidence

ORD record
ord-1224e2f15bf6412a90a4c53d4cc263a2
Source dataset
uspto-grants-2015_09
Patent number
US09145387B2

Reaction notes

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