Hydrochloric Acid → HCID 122512305, compound

HRID 1479079Notes

Reaction equation

HRID 1479079 reaction equation
Cl.C([O:6][C:7]([N:9]1[CH2:12][CH:11]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]([N:22]2[CH2:36][C:25]3=[C:26]4[N:31]([N:32]=[C:24]3[CH2:23]2)[C:30]([CH3:33])=[C:29]([Cl:34])[C:28]([CH3:35])=[N:27]4)=[O:21])[CH2:10]1)=[O:8])(C)(C)C>O1CCOCC1>[CH:7]([OH:8])=[O:6].[NH:9]1[CH2:12][CH:11]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]([N:22]2[CH2:36][C:25]3=[C:26]4[N:31]([N:32]=[C:24]3[CH2:23]2)[C:30]([CH3:33])=[C:29]([Cl:34])[C:28]([CH3:35])=[N:27]4)=[O:21])[CH2:10]1

Participants

4

Reactant 2

HCID 313Hydrochloric Acid2×HCID 131736551HCID 131736551, compound

Product 1

HCID 122512305HCID 122512305, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent3×

Procedure

A 4M solution of HCl in 1,4-dioxane (2.51 mL; 10.04 mmol; 5 eq.) was added to a solution of 3-[2-(6-chloro-5,7-dimethyl-1H,3H-2,4,7a,8-tetraaza-cyclopenta[a]indene-2-carbonyl)-phenoxy]-azetidine-1-carboxylic acid tert-butyl ester (1 g; 2.01 mmol; 1 eq.) in 1,4-dioxane (15 mL) and the resulting mixture was stirred at room temperature for 3.5 hours. A 4M solution of HCl in 1,4-dioxane (1 mL; 4 mmol; 2 eq.) was added and the reaction mixture was stirred at room temperature for 2.5 hours then concentrated in vacuo. The residue was taken up in water and the pH made basic. The solution was extracted with DCM and the organic layer dried over magnesium sulfate and concentrated in vacuo. Purification by mass directed preparative HPLC afforded the title compound (60 mg, 7%) as a white solid. 1H NMR (CDCl3) δ 8.41 (s, 1H), 7.40-7.33 (m, 4H), 7.14-7.07 (m, 1H), 6.66-6.62 (m, 1H), 5.13-5.07 (m, 1H), 4.97 (s, 2H), 4.59 (s, 2H), 4.29-4.23 (m, 2H), 3.97-3.92 (m, 2H), 2.88 (s, 2H), 2.83 (s, 1H), 2.67 (s, 1H), 2.60 (s, 2H). HPLC (max plot) 97.3%, Rt 2.45 min. UPLC/MS: (MS+) 398.4 ([M+H]+).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 2.5 hours
  2. concentrationthen concentrated in vacuo
  3. extractionThe solution was extracted with DCM
  4. dry with materialthe organic layer dried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification by mass

Sources & evidence

ORD record
ord-e0df54cc78f641f6bfc23a53bfaf0191
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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