Ammonium Chloride → HCID 67280019, compound

HRID 1693311Notes

Reaction equation

HRID 1693311 reaction equation
C(OC([N:8](C(OC(C)(C)C)=O)[C:9]1[C:10]2[C:11]3[C:12](=[N:23][N:24]([CH2:26][C:27]4[C:32]([CH3:33])=[C:31]([O:34][CH3:35])[C:30]([CH3:36])=[CH:29][N:28]=4)[N:25]=2)[CH:13]=[C:14]([CH2:19][C:20]([OH:22])=O)[C:15]=3[CH2:16][S:17][N:18]=1)=O)(C)(C)C.[Cl-].[NH4+].O.O[N:48]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>CN(C)C=O>[NH2:8][C:9]1[C:10]2[C:11]3[C:12](=[N:23][N:24]([CH2:26][C:27]4[C:32]([CH3:33])=[C:31]([O:34][CH3:35])[C:30]([CH3:36])=[CH:29][N:28]=4)[N:25]=2)[CH:13]=[C:14]([CH2:19][C:20]([NH2:48])=[O:22])[C:15]=3[CH2:16][S:17][N:18]=1

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67280836HCID 67280836, compound

Product 1

HCID 67280019HCID 67280019, compoundYield 99.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture composed of {4-[bis(tert-butoxycarbonyl)amino]-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-2,7-dihydro-6-thia-1,2,3,5-tetraazabenzo[cd]azulen-8-yl}acetic acid of Example 111 (24 mg), dimethylformamide (0.7 ml), ammonium chloride (13 mg), 1-hydroxybenzotriazole monohydrate (6 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (15 mg) and diisopropylethylamine (34 μl) was stirred at room temperature for three days. The solvent in the reaction mixture was evaporated by spraying, and a 0.2 N sodium hydroxide solution was added to the resulting residue, followed by extraction with ethyl acetate. The organic layer was concentrated under reduced pressure. Dichloromethane (2 ml) and trifluoroacetic acid (0.5 ml) were added to the resulting residue, and the mixture was stirred at room temperature for 20 hours. The reaction mixture was concentrated under reduced pressure. A saturated sodium bicarbonate solution was placed into the resulting residue, followed by extraction with chloroform. The organic layer was dried over sodium sulfate and filtered. Then, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel thin-layer chromatography (chloroform-methanol) to obtain the title compound (16.1 mg, 70%) as a solid.

Workup

  1. customThe solvent in the reaction mixture was evaporated
  2. additiona 0.2 N sodium hydroxide solution was added to the resulting residue
  3. extractionfollowed by extraction with ethyl acetate
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. additionDichloromethane (2 ml) and trifluoroacetic acid (0.5 ml) were added to the resulting residue
  6. stirringthe mixture was stirred at room temperature for 20 hours
  7. concentrationThe reaction mixture was concentrated under reduced pressure
  8. extractionfollowed by extraction with chloroform
  9. dry with materialThe organic layer was dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationThen, the filtrate was concentrated under reduced pressure
  12. customThe resulting residue was purified by silica gel thin-layer chromatography (chloroform-methanol)

Sources & evidence

ORD record
ord-c49252668fb14998bf866c0a9b36a514
Source dataset
uspto-grants-2012_04
Patent number
US08158638B2

Reaction notes

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