Hydrochloric Acid → HCID 89662806, compound

HRID 1479097Notes

Reaction equation

HRID 1479097 reaction equation
C(OC([N:8]1[CH2:14][CH2:13][CH2:12][C@@H:11]([O:15][C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[C:23]([N:25]2[CH2:39][C:28]3=[C:29]4[N:34]([N:35]=[C:27]3[CH2:26]2)[C:33]([CH3:36])=[C:32]([Cl:37])[C:31]([CH3:38])=[N:30]4)=[O:24])[CH2:10][CH2:9]1)=O)(C)(C)C.Cl>O1CCOCC1.[OH-].[Na+]>[NH:8]1[CH2:14][CH2:13][CH2:12][C@@H:11]([O:15][C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[C:23]([N:25]2[CH2:39][C:28]3=[C:29]4[N:34]([N:35]=[C:27]3[CH2:26]2)[C:33]([CH3:36])=[C:32]([Cl:37])[C:31]([CH3:38])=[N:30]4)=[O:24])[CH2:10][CH2:9]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 89649991HCID 89649991, compound

Product 1

HCID 89662806HCID 89662806, compoundYield 19%

Reagents, catalysts & solvents 2

HCID 14798Sodium HydroxideSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of (R)-4-[2-(6-chloro-5,7-dimethyl-1H,3H-2,4,7a,8-tetraaza-cyclopenta[a]indene-2-carbonyl)-5-fluoro-phenoxy]-azepane-1-carboxylic acid tert-butyl ester (173 mg; 0.31 mmol; 1 eq.) in a 4M solution of HCl in 1,4-dioxane (2 mL) was stirred at room temperature for 16 hours. The residue was diluted with 0.1M NaOH and extracted with DCM (2×). The combined organic phase was dried over magnesium sulfate and concentrated in vacuo. Purification by mass directed preparative HPLC afforded the title compound (27 mg, 17%) as a yellow solid. 1H NMR (DMSO-d6) δ 8.34 (s, 1H), 7.37 (ddd, J=8.5, 6.8, 3.2 Hz, 1H), 7.12 (dd, J=11.8, 2.3 Hz, 1H), 6.87 (td, J=8.4, 2.3 Hz, 1H), 4.88-4.72 (m, 2H), 4.54 (d, J=15.8 Hz, 2H), 3.10-2.74 (m, 7H), 2.61 (s, 1.5H), 2.56 (s, 1.5H), 2.11-1.49 (m, 6H). HPLC (max plot) 96.2%, Rt 2.91 min. UPLC/MS: (MS+) 458.4 ([M+H]+).

Workup

  1. extractionextracted with DCM (2×)
  2. dry with materialThe combined organic phase was dried over magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customPurification by mass

Sources & evidence

ORD record
ord-57043c5bacfe4019980085c8329f1377
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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