Hydrochloric Acid → HCID 122429367, compound

HRID 1479096Notes

Reaction equation

HRID 1479096 reaction equation
C([O:5][C:6]([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:7])(C)(C)C.Cl>O1CCOCC1.[OH-].[Na+]>[CH:6]([OH:7])=[O:5].[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 89650388HCID 89650388, compound

Product 1

HCID 122429367HCID 122429367, compoundYield 7%

Reagents, catalysts & solvents 2

HCID 14798Sodium HydroxideSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of (S)-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 (180 mg; 1.11 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 (38 mg, 7%) 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=11.7, 2.3 Hz, 1H), 6.88 (td, J=8.4, 2.3 Hz, 1H), 4.93-4.72 (m, 3H), 4.54 (d, J=15.1 Hz, 2H), 3.03-2.75 (m, 6.7H), 2.62 (s, 1.5H), 2.56 (s, 1.5H), 2.11-1.49 (m, 6.3H). HPLC (max plot) 90.3%, 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-8bee89e4f9614d53852f6cfe606cddd3
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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