Ethyl Acetate → HCID 71183354, compound

HRID 717054Notes

Reaction equation

HRID 717054 reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[CH:11][C:12]3[O:18][CH2:17][CH2:16][NH:15][C:14](=[O:19])[C:13]=3[CH:20]=2)=[CH:5][CH:4]=1.[H-].[Na+].Cl[CH2:26][C:27]1[N:28]=[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]2[CH:35]=1.C(OCC)(=O)C>C1COCC1>[N:28]1[C:27]([CH2:26][N:15]2[C:14](=[O:19])[C:13]3[CH:20]=[C:9]([C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:21])[F:22])=[CH:8][CH:7]=4)[CH:10]=[CH:11][C:12]=3[O:18][CH2:17][CH2:16]2)=[CH:35][N:30]2[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=12

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 9576142-Chloromethyl-imidazo(1,2-A)pyridineHCID 71150440HCID 71150440, compound

Product 1

HCID 71183354HCID 71183354, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

7-(4-(trifluoromethyl)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one (50 mg) was dissolved in dry THF and the NaH suspension (6 mg, 60% in oil) was added, followed shortly by 2-(chloromethyl)imidazo[1,2-a]pyridine (29 mg) and stirred overnight at room temperature. Worked up with ethyl acetate and pH 7 buffer organic layer dried over MgS(O)4 and concentrated. Purification was conducted on normal phase (CH2Cl2/10% EtOH in ethyl acetate gradient) followed by reverse-phase (ACN/H2O, 0.1% TFA). Resulting glassy solid was dissolved in dioxane, diluted 10-fold with 0.1N HCl and lyophilized resulting in 4-(imidazo[1,2-a]pyridin-2-ylmethyl)-7-(4-(trifluoromethyl)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one hydrochloride salt as a white solid (42.2 mg).

Workup

  1. dry with materialdried over MgS(O)4
  2. concentrationconcentrated
  3. customPurification
  4. dissolutionResulting glassy solid was dissolved in dioxane
  5. additiondiluted 10-fold with 0.1N HCl
  6. customlyophilized resulting in 4-(imidazo[1,2-a]pyridin-2-ylmethyl)-7-(4-(trifluoromethyl)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one hydrochloride salt as a white solid (42.2 mg)

Sources & evidence

ORD record
ord-87eadbc46b614e288ada5ff00a7cc706
Source dataset
uspto-grants-2015_11
Patent number
US09193694B2

Reaction notes

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