Acetyl chloride → HCID 86610609, compound

HRID 506377Notes

Reaction equation

HRID 506377 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[C:24]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=3)=[CH:23][C:22]([C:40]#[N:41])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:42][CH3:43])=[O:5])[CH3:2].[C:44](Cl)(=[O:46])[CH3:45].C(=O)([O-])[OH:49].[Na+].C(OCC)(=O)C>C(O)C>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[C:24]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:33])[F:34])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=3)=[CH:23][C:22]([C:40]([O:46][CH2:44][CH3:45])=[NH:41])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:42][CH3:43])=[O:5])[CH3:2].[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[C:24]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:33])[F:34])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=3)=[CH:23][C:22]([C:40](=[O:49])[NH2:41])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:42][CH3:43])=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 6367Acetyl chlorideHCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 86610610HCID 86610610, compound

Product 2

HCID 86610609HCID 86610609, compoundHCID 87546926HCID 87546926, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(2R*,4S*)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-cyanopyridin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (1.5 g) is dissolved in ethanol (30 ml) and thereto is added acetyl chloride (14 ml) at 0° C. dropwise. After addition dropwise, the mixture is stirred at room temperature overnight. A saturated aqueous sodium hydrogen carbonate solution and ethyl acetate are added to the reaction solution, the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; hexane:ethyl acetate=9:1→1:1) to give (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-(5-ethoxycarbonimidoylpyridin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (221 mg), [MS (m/z): 654 [M+H]+], (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-(5-carbamoylpyridin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (404 mg)[MS (m/z): 626 [M+H]+]and (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-(5-ethoxycarbonylpyridin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (596 mg)[MS (m/z): 655 [M+H]+].

Workup

  1. additionAfter addition dropwise
  2. washthe organic layer is washed with a saturated brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue is purified by column chromatography (silica gel; hexane:ethyl acetate=9:1→1:1)

Sources & evidence

ORD record
ord-e087ed6bdf0942a4bc57838143c24004
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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