Acryloyl chloride → HCID 86677323, compound

HRID 1842822Notes

Reaction equation

HRID 1842822 reaction equation
[C:1](Cl)(=[O:4])[CH:2]=[CH2:3].[NH2:6][C:7]1[CH:12]=[C:11]([NH:13][C:14]2[N:19]=[C:18]([C:20]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]([CH3:29])[CH:21]=3)[CH:17]=[CH:16][N:15]=2)[C:10]([O:30][CH3:31])=[CH:9][C:8]=1[N:32]([CH3:44])[CH2:33][CH2:34][N:35]([CH3:43])[C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39].CCN(C(C)C)C(C)C>C(Cl)Cl.CO>[CH3:31][O:30][C:10]1[C:11]([NH:13][C:14]2[N:19]=[C:18]([C:20]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]([CH3:29])[CH:21]=3)[CH:17]=[CH:16][N:15]=2)=[CH:12][C:7]([NH:6][C:1](=[O:4])[CH:2]=[CH2:3])=[C:8]([N:32]([CH3:44])[CH2:33][CH2:34][N:35]([CH3:43])[C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:39])[CH3:40])[CH:9]=1

Participants

6

Reactant 3

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 86677348HCID 86677348, compound2×

Product 1

HCID 86677323HCID 86677323, compoundYield 78.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Procedure

Acryloyl chloride (0.069 mL, 0.85 mmol) in CH2Cl2 (2.5 mL) was added dropwise over 5 minutes to a solution of tert-butyl N-[2-[[2-amino-5-methoxy-4-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]-methylamino]ethyl]-N-methylcarbamate (Intermediate 171, 377 mg, 0.71 mmol) and DIPEA (0.234 mL, 1.42 mmol) in CH2Cl2 (8 mL) cooled in an ice/methanol bath. The mixture was stirred for 0.5 h. The mixture was then diluted with 10% CH3OH in CH2Cl2. The resulting solution was washed with sat. NaHCO3, dried (MgSO4) and then concentrated in vacuo. Purification by FCC, eluting with 0-3% CH3OH in CH2Cl2 gave the title compound (325 mg, 78%) as a yellow foam; 1H NMR: 1.38 (9H, s), 2.71 (3H, s), 2.77 (3H, s), 3.00 (2H, t), 3.34 (2H, t), 3.88 (3H, s), 3.91 (3H, s), 5.73-5.78 (1H, m), 6.27 (1H, dd), 6.67 (1H, dd), 6.99 (1H, s), 7.17 (1H, t), 7.21-7.27 (2H, m), 7.53 (1H, d), 7.87 (1H, s), 8.26 (1H, d), 8.33 (1H, d), 8.62 (1H, s), 8.99 (1H, s), 9.10 (1H, s); m/z: ES+ MH+ 584.73.

Workup

  1. temperaturecooled in an ice/methanol bath
  2. washThe resulting solution was washed with sat. NaHCO3
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customPurification by FCC
  6. washeluting with 0-3% CH3OH in CH2Cl2

Sources & evidence

ORD record
ord-ce37ba865c7e48d69de2ef55f7976b58
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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