Ethyl Acetate → HCID 131736987, compound

HRID 58204Notes

Reaction equation

HRID 58204 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([N:47]2[CH2:52][CH2:51][N:50]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:49][CH2:48]2)[CH:5]=[CH:6][C:7]=1[N:8]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[C:9]1[CH:14]=[C:13]([N:15]([CH3:39])[C:16]([N:18]([C:27]2[C:32]([Cl:33])=[C:31]([O:34][CH3:35])[CH:30]=[C:29]([O:36][CH3:37])[C:28]=2[Cl:38])[CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])=[O:17])[N:12]=[CH:11][N:10]=1.CCN(C(C)C)C(C)C.[C:69](Cl)(=[O:72])[CH:70]=[CH2:71].CCOC(C)=O>C1COCC1.[Cl-].[Na+].O>[C:69]([NH:1][C:2]1[CH:3]=[C:4]([N:47]2[CH2:52][CH2:51][N:50]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:49][CH2:48]2)[CH:5]=[CH:6][C:7]=1[N:8]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[C:9]1[CH:14]=[C:13]([N:15]([CH3:39])[C:16]([N:18]([C:27]2[C:28]([Cl:38])=[C:29]([O:36][CH3:37])[CH:30]=[C:31]([O:34][CH3:35])[C:32]=2[Cl:33])[CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:24])[CH3:25])=[O:17])[N:12]=[CH:11][N:10]=1)(=[O:72])[CH:70]=[CH2:71]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 131736986HCID 131736986, compound

Product 1

HCID 131736987HCID 131736987, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Crude tert-butyl 4-(3-amino-4-((tert-butoxycarbonyl)(6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methyl-3-((2-(trimethylsilyl)ethoxy)methyl)ureido)pyrimidin-4-yl)amino)phenyl)piperazine 1-carboxylate (95 g, 0.11 mmol) was dissolved in THF (1.5 ml) and stirred over ice bath under nitrogen atmosphere. DIEA (57 μl, 0.30 mmol) followed by acryloyl chloride (13 μl, 0.16 mmol) were added and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into EtOAc and brine. The organic. layer was separated, dried over MgSO4 and evaporated. The resulting material was purified by flash chromatography on silica eluting with 30% to 100% EtOAc/Hexane to afford the title compound (47 mg, yield: 47%). 1H-NMR (400 MHz, CDCl3) δ 0.02 (s, 9H) 0.79-1.04 (m, 2H) 1.36 (s, 9H) 1.49 (s, 9H) 3.08 (s, 4H) 3.05 (s, 3H) 3.25 (br. s., 4H) 3.64 (br. s., 4H) 3.86 (s, 6H) 5.27 (s, 1H) 5.67-5.79 (m, 1H) 6.15-6.56 (m, 2H) 6.48 (s, 1H) 7.03-7.14 (m, 1H) 7.87-8.09 (m, 2H) 8.19-8.29 (br. s., 1H) 8.44 (s, 1H).

Workup

  1. additionwere added
  2. stirringthe reaction mixture was stirred at room temperature for 1 hour
  3. customlayer was separated
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe resulting material was purified by flash chromatography on silica eluting with 30% to 100% EtOAc/Hexane

Sources & evidence

ORD record
ord-89219b2df7864a6293a6e352e2990f31
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

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