HCID 21962576, compound → HCID 21962570, compound

HRID 353038Notes

Reaction equation

HRID 353038 reaction equation
[CH2:1]([O:8][C:9]([N:11]([CH2:19][CH2:20][CH2:21][N:22]1[C:27]2[CH:28]=[CH:29][C:30]([S:32][CH:33]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:31][C:26]=2[O:25][CH2:24][C:23]1=[O:46])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N+:13]=1[O-])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>O1CCCC1.[Ti](Cl)(Cl)(Cl)Cl>[CH2:1]([O:8][C:9]([N:11]([CH2:19][CH2:20][CH2:21][N:22]1[C:27]2[CH:28]=[CH:29][C:30]([S:32][CH:33]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:31][C:26]=2[O:25][CH2:24][C:23]1=[O:46])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 1

HCID 21962576HCID 21962576, compound

Product 1

HCID 21962570HCID 21962570, compound

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of titanium (IV) chloride in tetrahydrofuran under nitrogen atmosphere, is added and equimolar amount of stannous chloride dihydrate, and the mixture is stirred 1 hour at room temperature. Then, a solution of ethyl 3-[(4-{3-[N-benzyloxycarbonyl-N-(1-oxido-2-pyridinyl)amino]propyl}-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)sulfanyl]-3-phenylpropanoate is added and the mixture heated 3 hours at 40° C. After evaporation of the solvent, ice and aqueous sodium bicarbonate are added, the mixture extracted with ethyl acetate, and the organic layers are combined and dried over sodium sulfate. The solvent is evaporated and ethyl 3-[(4-{3-[N-benzyloxycarbonyl-N-(2-pyridinyl)amino]-propyl}-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)sulfanyl]-3-phenylpropanoate is isolated by column chromatography. A solution of ethyl 3-[(4-{3-[N-benzyloxycarbonyl-N-(2-pyridinyl)amino]-propyl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)sulfanyl]-3-phenylpropanoate in acetic acid is treated with a solution of 30% hydrobromic acid in acetic acid at room temperature overnight. The solvent is evaporated under reduced pressure, and the residue is treated with a saturated sodium bicarbonate solution. The aqueous mixture is extracted with dichloromethane. The organic extracts are dried over sodium sulfate, evaporated to small volume and the product is purified by flash chromatography

Workup

  1. customAfter evaporation of the solvent, ice and aqueous sodium bicarbonate
  2. additionare added
  3. extractionthe mixture extracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. customThe solvent is evaporated

Sources & evidence

ORD record
ord-f21d90609d8b444c905ca7549f1ddd9c
Source dataset
uspto-grants-2004_06
Patent number
US06750215B2

Reaction notes

Loading…