Hydrochloric Acid → N-[5-Cyano-4-[(2-methoxyethyl)amino]-2-pyridinyl]-7-formyl-3,4-dihydro-6-[[(3S)-3-hydroxy-2-oxo-1-pyrrolidinyl]methyl]-1,8-naphthyridine-1(2H)-carboxamide

HRID 1778097Notes

Reaction equation

HRID 1778097 reaction equation
Cl.[Si]([O:9][C@H:10]1[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:17]=[C:18]3[C:23](=[N:24][C:25]=2[CH:26](OC)[O:27]C)[N:22]([C:31]([NH:33][C:34]2[CH:39]=[C:38]([NH:40][CH2:41][CH2:42][O:43][CH3:44])[C:37]([C:45]#[N:46])=[CH:36][N:35]=2)=[O:32])[CH2:21][CH2:20][CH2:19]3)[C:11]1=[O:47])(C(C)(C)C)(C)C.C([O-])(O)=O.[Na+].CCOC(C)=O>C1COCC1.O.CCCCCCC.C(Cl)Cl>[C:45]([C:37]1[C:38]([NH:40][CH2:41][CH2:42][O:43][CH3:44])=[CH:39][C:34]([NH:33][C:31]([N:22]2[C:23]3[C:18](=[CH:17][C:16]([CH2:15][N:12]4[CH2:13][CH2:14][C@H:10]([OH:9])[C:11]4=[O:47])=[C:25]([CH:26]=[O:27])[N:24]=3)[CH2:19][CH2:20][CH2:21]2)=[O:32])=[N:35][CH:36]=1)#[N:46]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 131734803(S)-6-((3-((tert-butyldimethylsilyl)oxy)-2-oxopyrrolidin-1-yl)methyl)-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide2×

Product 1

HCID 118036461N-[5-Cyano-4-[(2-methoxyethyl)amino]-2-pyridinyl]-7-formyl-3,4-dihydro-6-[[(3S)-3-hydroxy-2-oxo-1-pyrrolidinyl]methyl]-1,8-naphthyridine-1(2H)-carboxamide

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8900HeptaneSolvent

Procedure

Concentrated hydrochloric acid (0.66 ml) was added to a solution of (S)-6-((3-((tert-butyldimethylsilyl)oxy)-2-oxopyrrolidin-1-yl)methyl)-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 80C, 525 mg, 0.803 mmol) in THF (10 ml) and water (2 ml) at room temperature. After stirring for 15 h at room temperature saturated aqueous NaHCO3 was added, the mixture extracted with DCM (3×), the organic layers dried over Na2SO4 and evaporated. The residue was sonicated with EtOAc (6 ml) and pentane (6 ml) and then filtered. The white solid obtained was then heated and stirred with EtOAc (7 ml) and DCM (3 ml) for 30 minutes. The mixture was cooled, heptane (10 ml) added and the suspension filtered to give the title compound as a white solid.

Workup

  1. additionwas added
  2. extractionthe mixture extracted with DCM (3×)
  3. dry with materialthe organic layers dried over Na2SO4
  4. customevaporated
  5. customThe residue was sonicated with EtOAc (6 ml) and pentane (6 ml)
  6. filtrationfiltered
  7. customThe white solid obtained
  8. temperaturewas then heated
  9. temperatureThe mixture was cooled
  10. filtrationthe suspension filtered

Sources & evidence

ORD record
ord-8fd9103ab253421193ee1893e058bdcd
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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