Methanol → HCID 68472339, compound

HRID 2061840Notes

Reaction equation

HRID 2061840 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:17]3[CH:18]=[N:19][C:20]([NH:32][C:33]([NH:35][CH2:36][CH3:37])=[O:34])=[CH:21][C:22]=3[C:23]3[S:24][CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[N:27]=3)[CH:13]=2)[N:8]([CH2:38][C@@H:39]2[CH2:44][O:43][CH2:42][CH2:41][N:40]2[C:45]([O:47]C(C)(C)C)=[O:46])[CH:7]=1)=[O:5])[CH3:2].[CH2:52]1[CH2:56]OC[CH2:53]1.[Li+].[OH-].[CH3:59]O>>[C:52]([C@@:39]1([CH2:38][N:8]2[C:9]3[C:14](=[CH:13][C:12]([C:17]4[CH:18]=[N:19][C:20]([NH:32][C:33]([NH:35][CH2:36][CH3:37])=[O:34])=[CH:21][C:22]=4[C:23]4[S:24][CH:25]=[C:26]([C:28]([F:30])([F:29])[F:31])[N:27]=4)=[CH:11][CH:10]=3)[C:15](=[O:16])[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:7]2)[CH2:44][O:43][CH2:42][CH2:41][N:40]1[C:45]([OH:47])=[O:46])([CH3:53])([CH3:56])[CH3:59]

Participants

5

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 68473203HCID 68473203, compound

Product 1

HCID 68472339HCID 68472339, compoundYield 36%

Conditions

Temperature
100 °C

Procedure

(R)-tert-butyl 3-((3-(ethoxycarbonyl)-6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-4-oxoquinolin-1(4H)-yl)methyl)morpholine-4-carboxylate (Example 254, 0.150 g, 0.20 mmol) was suspended in MeOH (6 mL) in a microwave vessel (CEM). THF (3.00 mL) was added. A 2.0 M aq solution of LiOH (0.381 mL, 0.76 mmol) was added. The microwave vessel was heated in the microwave at 100° C. for 15 min After cooling to room temperature solvent was removed in vacuo and residue was taken up in dichloromethane (2 ml) and 4N HCl in dioxane (1 ml) was added. The mixture was stirred at room temperature for 1 h, then diluted with water (3 ml) and neutralized with saturate NaHCO3. The mixture was extracted with DCM three times, and the combined organic layers were dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel using (dichloromethane-methanol) to give (R)-tert-butyl 3-((3-(ethoxycarbonyl)-6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-4-oxoquinolin-1(4H)-yl)methyl)morpholine-4-carboxylic acid (0.042 g, 36%).

Workup

  1. temperatureAfter cooling to room temperature solvent
  2. customwas removed in vacuo and residue
  3. addition4N HCl in dioxane (1 ml) was added
  4. additiondiluted with water (3 ml)
  5. extractionThe mixture was extracted with DCM three times
  6. dry with materialthe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by flash column chromatography on silica gel using (dichloromethane-methanol)

Sources & evidence

ORD record
ord-6da665ef63de451bbe209f3ec8098d1c
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

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