Toluene → HCID 58215614, compound

HRID 1630822Notes

Reaction equation

HRID 1630822 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[NH:8][C:9]3[C:14]([CH:15]=2)=[CH:13][C:12]([C:16]#[N:17])=[CH:11][CH:10]=3)[CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.[C:35]([O:41][CH2:42]Cl)(=[O:40])[C:36]([CH3:39])([CH3:38])[CH3:37].C(=O)(O)[O-].[Na+]>C1COCC1>[C:16]([C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:42][O:41][C:35](=[O:40])[C:36]([CH3:39])([CH3:38])[CH3:37])[C:7]([C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)=[CH:15]2)#[N:17]

Participants

7

Reactant 5

HCID 1140TolueneHCID 87885Chloromethyl pivalateHCID 516892Sodium BicarbonateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 445541352-pyridin-3-yl-1H-indole-5-carbonitrile

Product 1

HCID 58215614HCID 58215614, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-pyridin-3-yl-1H-indole-5-carbonitrile (Example 8, 210 mg, 1.37 mmol) in THF (20 mL) at room temperature is added 0.5 M KHMDS in toluene (4.1 mL, 2.05 mmol). After 30 min, chloromethyl pivalate (510 mg, 3.08 mmol) is added. The mixture is stirred under N2 for 1 h. Saturated aqueous sodium bicarbonate (0.5 mL) is added to quench the reaction. Silica gel is added to the mixture and the solvents are removed in vacuo. The residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:0). Further purification by HPLC using an Xbridge RP18 with a gradient of 0.1% aqueous ammonium hydroxide in acetonitrile gives 2,2-dimethyl-propionic acid 5-cyano-2-pyridin-3-yl-indol-1-ylmethyl ester as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.20 (s, 9H), 6.08 (s, 2H), 6.77 (s, 1H), 7.49 (ddd, J=7.8, 4.8, 0.8 Hz, 1H), 7.56 (dd, J=8.6, 1.8 Hz, 1H), 7.68 (d, J=8.6 Hz, 1H), 7.94 (ddd, J=7.9, 2.0 Hz, 1H), 8.01 (dd, J=1.5, 0.5 Hz, 1H), 8.75 (dd, J=4.8, 1.8 Hz, 1H), 8.87 (d, J=1.5 Hz, 1H). HRMS (ESI) m/z 334.1566 [(M+H)+ Calcd for C20H20N3O2: 334.1556].

Workup

  1. customto quench
  2. customthe reaction
  3. additionSilica gel is added to the mixture
  4. customthe solvents are removed in vacuo
  5. customThe residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:0)
  6. customFurther purification by HPLC

Sources & evidence

ORD record
ord-a20e284aa97d463383137314b49154ef
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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