Ethyl cyanoacetate → HCID 86675925, compound

HRID 572671Notes

Reaction equation

HRID 572671 reaction equation
Cl.[F:2][C:3]1[CH:30]=[CH:29][C:6]([CH2:7][NH:8][C:9]([C:11]2[CH:16]=[C:15]([C:17]3[CH2:21][CH:20]([CH:22]4[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)[O:19][N:18]=3)[N:14]=[C:13]([CH3:28])[N:12]=2)=[O:10])=[CH:5][C:4]=1[O:31][CH3:32].C(N(CC)CC)C.[C:40]([CH2:42][C:43](OCC)=[O:44])#[N:41]>O>[C:40]([CH2:42][C:43]([N:25]1[CH2:24][CH2:23][CH:22]([CH:20]2[O:19][N:18]=[C:17]([C:15]3[N:14]=[C:13]([CH3:28])[N:12]=[C:11]([C:9]([NH:8][CH2:7][C:6]4[CH:29]=[CH:30][C:3]([F:2])=[C:4]([O:31][CH3:32])[CH:5]=4)=[O:10])[CH:16]=3)[CH2:21]2)[CH2:27][CH2:26]1)=[O:44])#[N:41]

Participants

5

Reactant 3

HCID 7764Ethyl cyanoacetateHCID 8471TriethylamineHCID 71466164HCID 71466164, compound

Product 1

HCID 86675925HCID 86675925, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A 100 mL sealed tube was charged with N-(4-fluoro-3-methoxybenzyl)-2-methyl-6-(5-(piperidin-4-yl)-4,5-dihydroisoxazol-3-yl)pyrimidine-4-carboxamide hydrochloride (0.15 g, 0.32 mmol, Preparation #K.1), triethyl amine (0.163 g, 1.6 mmol, Sd Fine Chem), and ethyl cyanoacetate (0.54 mL, 4.8 mmol). The reaction mixture was heated at about 150° C. for about 12 h, cooled to RT and water (15 mL) was added. The product was extracted with EtOAc (2×15 mL). The combined organic layer was dried over sodium sulphate and concentrated under reduced pressure. The crude material obtained was purified by preparative HPLC (Table 2, Method d) to afford 6-(5-(1-(2-cyanoacetyl)piperidin-4-yl)-4,5-dihydroisoxazol-3-yl)-N-(4-fluoro-3-methoxybenzyl)-2-methylpyrimidine-4-carboxamide as an off white solid 0.065 g (40.8%). LC/MS (Table 1, Method c) Rt=1.38 min; MS m/z: 495.3 (M+H)+.

Workup

  1. customA 100 mL sealed tube
  2. temperaturecooled to RT
  3. extractionThe product was extracted with EtOAc (2×15 mL)
  4. dry with materialThe combined organic layer was dried over sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material obtained
  7. customwas purified by preparative HPLC (Table 2, Method d)

Sources & evidence

ORD record
ord-efd60254489e4a7fae32c5e05ac6aa85
Source dataset
uspto-grants-2015_05
Patent number
US09029409B2

Reaction notes

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