Pentafluorophenyl acrylate → HCID 73292362, compound

HRID 1842626Notes

Reaction equation

HRID 1842626 reaction equation
[C:1](OC1C(F)=C(F)C(F)=C(F)C=1F)(=[O:4])[CH:2]=[CH2:3].[CH3:17][O:18][C:19]1[CH:24]=[C:23]([N:25]2[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]2)[C:22]([NH2:32])=[CH:21][C:20]=1[NH:33][C:34]1[N:39]=[C:38]([C:40]2[CH:41]=[N:42][N:43]3[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=23)[CH:37]=[CH:36][N:35]=1>CN(C=O)C.C(Cl)Cl>[CH3:17][O:18][C:19]1[C:20]([NH:33][C:34]2[N:39]=[C:38]([C:40]3[CH:41]=[N:42][N:43]4[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=34)[CH:37]=[CH:36][N:35]=2)=[CH:21][C:22]([NH:32][C:1](=[O:4])[CH:2]=[CH2:3])=[C:23]([N:25]2[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]2)[CH:24]=1

Participants

5

Reactant 2

HCID 2775973Pentafluorophenyl acrylateHCID 86677250HCID 86677250, compound2×

Product 1

HCID 73292362HCID 73292362, compoundYield 29.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

(2,3,4,5,6-Pentafluorophenyl) prop-2-enoate (0.030 mL, 0.19 mmol) was added dropwise to a solution of 4-methoxy-6-(4-methylpiperazin-1-yl)-N′(4-pyrazolo[1,5-a]-pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamine (Intermediate 69, 67 mg, 0.16 mmol) in DMF (0.6 mL) at r.t. under N2. The resulting solution was stirred at r.t. for 1.5 h and then diluted with CH2Cl2 (9 mL). This solution was added to 1.5 g flash silica which was wet with CH2Cl2 in a dry-loaded cartridge, and the crude product was eluted from the silica using CH2Cl2. Further purification by FCC, eluting with 2-7% of 2N methanolic ammonia in CH2Cl2 provided material which was further purified by FCC, eluting with 5-20% CH3OH in CH2Cl2. Appropriate fractions were concentrated in vacuo and trituration provided a crystalline solid that was washed with THF (0.1 mL) to give the title compound (23 mg, 28%) as a beige crystalline solid; 1H NMR: 2.33-2.43 (3H, m), 2.62-2.81 (4H, m), 2.94 (4H, s), 3.85 (3H, s), 5.72 (1H, d), 6.18 (1H, m), 6.55-6.69 (1H, m), 6.89 (1H, s), 7.05 (1H, m), 7.26 (1H, d), 7.35-7.43 (1H, m), 8.15 (1H, s), 8.34 (1H, d), 8.44 (1H, d), 8.49 (1H, s), 8.79 (1H, d), 8.80 (1H, s), 9.03 (1H, s); m/z: ES+ MH+ 485.

Workup

  1. additionThis solution was added to 1.5 g flash silica which
  2. washthe crude product was eluted from the silica
  3. customFurther purification by FCC
  4. washeluting with 2-7% of 2N methanolic ammonia in CH2Cl2 provided material which
  5. customwas further purified by FCC
  6. washeluting with 5-20% CH3OH in CH2Cl2
  7. concentrationAppropriate fractions were concentrated in vacuo and trituration
  8. customprovided a crystalline solid
  9. washthat was washed with THF (0.1 mL)

Sources & evidence

ORD record
ord-e4b99a6e0fa747169e8400ac15350ee2
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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