Lithium Hydroxide → 7-[2-(Ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]-2-methyl-3-oxo-4H-pyrido[3,2-b][1,4]oxazine-2-carboxylic acid

HRID 712317Notes

Reaction equation

HRID 712317 reaction equation
[CH2:1]([NH:3][C:4](=[O:38])[NH:5][C:6]1[S:7][C:8]2[C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)=[CH:13][C:12]([C:21]3[CH:30]=[N:29][C:28]4[NH:27][C:26](=[O:31])[C:25]([CH3:37])([C:32]([O:34]CC)=[O:33])[O:24][C:23]=4[CH:22]=3)=[CH:11][C:9]=2[N:10]=1)[CH3:2].[Li+].[OH-]>C1COCC1>[CH2:1]([NH:3][C:4]([NH:5][C:6]1[S:7][C:8]2[C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)=[CH:13][C:12]([C:21]3[CH:30]=[N:29][C:28]4[NH:27][C:26](=[O:31])[C:25]([CH3:37])([C:32]([OH:34])=[O:33])[O:24][C:23]=4[CH:22]=3)=[CH:11][C:9]=2[N:10]=1)=[O:38])[CH3:2]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 86664029Ethyl 7-(2-(3-ethylureido)-7-(pyridin-2-yl)benzothiazol-5-yl)-2-methyl-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-2-carboxylate

Product 1

HCID 866640307-[2-(Ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]-2-methyl-3-oxo-4H-pyrido[3,2-b][1,4]oxazine-2-carboxylic acidYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice-cold solution of ethyl 7-(2-(3-ethylureido)-7-(pyridin-2-yl)benzothiazol-5-yl)-2-methyl-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-2-carboxylate (0.10 g, 0.19 mmol) in THF was added LiOH (0.023 g, 0.57 mmol dissolved in minimum amount of H2O) and the mixture stirred at rt for 3 h. After completion of reaction (by TLC), the solvent was concentrated and 10 mL of water added to the reaction. The aqueous layer was washed with EtOAc (2×50 mL) and the organic layer discarded. The pH of the aqueous layer was adjusted up to 4-5, extracted with hot EtOAc (3×50 mL) and the combined organic layer dried over Na2SO4, filtered and concentrated under reduced pressure. The residue thus obtained was triturated with ether to afford Compound 190 as an off-white solid (0.06 g, 63%). 1H NMR (DMSO-d6): δ 1.11 (t, J=7.20 Hz, 3H), 1.74 (s, 3H), 3.21 (m, 2H), 6.86 (br s, 1H), 7.44 (m, 1H), 7.97-8.06 (m, 3H), 8.28 (s, 1H), 8.50 (s, 1H), 8.56 (d, J=8.0 Hz, 1H), 8.81 (d, J=4.0 Hz, 1H), 10.63 (br s, 1H) and 11.57 (br s, 1H). MS: 505.29 [M+H]+.

Workup

  1. customAfter completion of reaction (by TLC)
  2. concentrationthe solvent was concentrated
  3. addition10 mL of water added to the reaction
  4. washThe aqueous layer was washed with EtOAc (2×50 mL)
  5. extractionextracted with hot EtOAc (3×50 mL)
  6. dry with materialthe combined organic layer dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue thus obtained
  10. customwas triturated with ether

Sources & evidence

ORD record
ord-e66f498a62304cc0bff664aed57363f0
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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