Acryloyl chloride → HCID 86677276, compound

HRID 1842643Notes

Reaction equation

HRID 1842643 reaction equation
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[CH3:6][O:7][C:8]1[CH:13]=[C:12]([N:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)[C:11]([NH2:21])=[CH:10][C:9]=1[NH:22][C:23]1[N:28]=[C:27]([C:29]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[N:31]([CH3:38])[CH:30]=2)[CH:26]=[CH:25][N:24]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:6][O:7][C:8]1[C:9]([NH:22][C:23]2[N:28]=[C:27]([C:29]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:31]([CH3:38])[CH:30]=3)[CH:26]=[CH:25][N:24]=2)=[CH:10][C:11]([NH:21][C:1](=[O:4])[CH:2]=[CH2:3])=[C:12]([N:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)[CH:13]=1

Participants

5

Reactant 3

HCID 13140Acryloyl chloride2×HCID 81531Diisopropylethylamine2×HCID 86677277HCID 86677277, compound2×

Product 1

HCID 86677276HCID 86677276, compoundYield 17.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Conditions

Temperature
0 °C

Procedure

A solution of acryloyl chloride (58.4 mg, 0.64 mmol) in CH2Cl2 (1 mL) was added dropwise to a mixture of 4-methoxy-N′-[4-(1-methylindol-3-yl)pyrimidin-2-yl]-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine (Intermediate 110, 286 mg, 0.64 mmol) and DIPEA (0.134 mL, 0.77 mmol) in CH2Cl2 (20 mL), which was cooled in an ice/water bath. The mixture was stirred for 1.5 h at 0° C. More DIPEA was added (30 μL) then more acryloyl chloride (20 mg) was added dropwise as a solution in CH2Cl2 (1 mL). This mixture was stirred for 2 h and then diluted with CH2Cl2 (50 mL). This solution was washed with sat. NaHCO3 solution (2×25 mL) and then the combined aqueous washes were extracted with CH2Cl2 (2×25 mL). The combined organic solutions were washed with brine, dried (MgSO4) and concentrated in vacuo. The resulting gum was triturated with diethyl ether to give a solid which was collected by filtration and dried in vacuo. Purification by FCC, eluting with 0-8% 7N methanolic ammonia in CH2Cl2 gave the title compound (55 mg, 17%) as a light grey solid after trituration with diethyl ether (with a few drops of CH3OH); 1H NMR: 2.27 (3H, s), 2.53-2.59 (4H, m), 2.85-2.91 (4H, m), 3.87 (3H, s), 3.91 (3H, s), 5.75 (1H, d), 6.24 (1H, d), 6.67 (1H, dd), 6.89 (1H, s), 7.15-7.28 (3H, m), 7.53 (1H, d), 7.89 (1H, s), 8.28 (1H, d), 8.32 (1H, d), 8.58 (1H, s), 8.81 (1H, s), 9.07 (1H, s); m/z: ES+ MH+ 498.58.

Workup

  1. temperaturewas cooled in an ice/water bath
  2. stirringThis mixture was stirred for 2 h
  3. washThis solution was washed with sat. NaHCO3 solution (2×25 mL)
  4. extractionthe combined aqueous washes were extracted with CH2Cl2 (2×25 mL)
  5. washThe combined organic solutions were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe resulting gum was triturated with diethyl ether
  9. customto give a solid which
  10. filtrationwas collected by filtration
  11. customdried in vacuo
  12. customPurification by FCC
  13. washeluting with 0-8% 7N methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-696ccfb71b6b492f846e701814691bb4
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

Loading…