Hydrochloric Acid → 2-((9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetraazatricyclo(8.3.0.0,2,6)trideca-2(6),4,7,10,12-pentaen-9-yl)acetic acid

HRID 874469Notes

Reaction equation

HRID 874469 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2=[N:9][C@@H:10]([CH2:24][C:25]([O:27]C)=[O:26])[C:11]3[N:12]([C:20]([CH3:23])=[N:21][N:22]=3)[C:13]3[S:17][C:16]([CH3:18])=[C:15]([CH3:19])[C:14]2=3)=[CH:4][CH:3]=1.O.[OH-].[Li+].Cl>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2=[N:9][C@@H:10]([CH2:24][C:25]([OH:27])=[O:26])[C:11]3[N:12]([C:20]([CH3:23])=[N:21][N:22]=3)[C:13]3[S:17][C:16]([CH3:18])=[C:15]([CH3:19])[C:14]2=3)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 59190723MS417

Product 1

HCID 668281072-((9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetraazatricyclo(8.3.0.0,2,6)trideca-2(6),4,7,10,12-pentaen-9-yl)acetic acidYield 87%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl 2-((6S,Z)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate (see e.g., WO 2006129623)(100.95 mg, 0.243 mmol was suspended in 1 mL methanol to which was added a freshly prepared solution of lithium hydroxide monohydrate (0.973 mL, 0.5 M, 0.487 mmol) and shaken at ambient temperature for 3 hours. The methanol was evaporated and the pH adjusted with aqueous hydrochloric acid (1 M, 0.5 mL, 0.5 mmol) and extracted four times with ethyl acetate. The combined ethyl acetate layers were dried over magnesium sulfate and evaporated to afford 2-((6S,Z)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetic acid (85.3 mg, 87.0%); ESI-MS m/z=401.1 [(M+H)+] which was used directly in the next reaction.

Workup

  1. customThe methanol was evaporated
  2. extractionextracted four times with ethyl acetate
  3. dry with materialThe combined ethyl acetate layers were dried over magnesium sulfate
  4. customevaporated

Sources & evidence

ORD record
ord-0d2b30a940eb43fca802612b19c6cb7b
Source dataset
uspto-grants-2015_03
Patent number
US08980879B2

Reaction notes

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