Hydrochloric Acid → HCID 135518301, compound

HRID 2245577Notes

Reaction equation

HRID 2245577 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH:3]=1.[O:17]=[C:18]1[CH2:26][C:25]2[C:20](=[CH:21][C:22]([C:27]#[N:28])=[CH:23][CH:24]=2)[NH:19]1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl>C(#N)CCC.ClCCl.CO.C(OCC)C>[ClH:1].[OH:17][C:18]1[NH:19][C:20]2[C:25]([C:26]=1[C:2]1[CH:3]=[C:4]([O:8][CH2:9][CH2:10][N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[N:5]=[CH:6][N:7]=1)=[CH:24][CH:23]=[C:22]([C:27]#[N:28])[CH:21]=2

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 27733482-Oxindole-6-carbonitrileHCID 85873129HCID 85873129, compound

Product 1

HCID 135518301HCID 135518301, compoundYield 19.1%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8008ButyronitrileSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 4-{2-[(6-chloropyrimidin-4-yl)oxy]ethyl}morpholine (0.116 g, 0.47 mmol), 2-oxoindoline-6-carbonitrile (0.075 g, 0.47 mmol) and cesium carbonate (0.46 g, 1.42 mmol) in butyronitrile (3 mL), was heated in a microwave oven at 160° C. for 10 min. The crude product was purified using preparative HPLC (XTerra®PrepMS C8 column 10 μm, 30×150 mm; 0.1 M NH4OAc buffer/acetonitrile, (80:20-20:80), as the eluent). The acetonitrile was evaporated and the remaining aqueous phase was extracted with chloroform and evaporated in vacuo to give a yellow solid. The solid was dissolved in dichloromethane/methanol, (9:1), and treated with HCl in diethyl ether (1 M) at 0° C. The resulting yellow crystals were collected by filtration, washed with diethyl ether, and dried to obtain 0.036 g (17% yield) of the title compound: 1H NMR (D2O, 400 MHz) δ 8.31 (s, 1H), 7.15 (dd, J=8, 2 Hz, 1H), 6.96 (d, J=8 Hz, 1H), 6.93 (d, J=2 Hz, 1H), 6.01 (s, 1H), 4.67 (m, 2H), 4.17 (m, 2H), 3.94 (m, 2H), 3.75 (m, 2H), 3.66 (m, 2H), 3.40 (m, 2H); MS (ESP) m/z 366 (M++1).

Workup

  1. customThe crude product was purified
  2. customThe acetonitrile was evaporated
  3. extractionthe remaining aqueous phase was extracted with chloroform
  4. customevaporated in vacuo
  5. customto give a yellow solid
  6. filtrationThe resulting yellow crystals were collected by filtration
  7. washwashed with diethyl ether
  8. customdried

Sources & evidence

ORD record
ord-7e6844d85bce470580badfe28092eb76
Source dataset
uspto-grants-2010_03
Patent number
US07683067B2

Reaction notes

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