Hydrochloric Acid → HCID 89662771, compound

HRID 1479107Notes

Reaction equation

HRID 1479107 reaction equation
Cl.C(OC([N:9]1[CH2:14][CH2:13][C@@H:12]([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])[CH2:11][C@@H:10]1[C:40]([F:43])([F:42])[F:41])=O)(C)(C)C.[OH-].[Na+]>O1CCOCC1>[Cl:37][C:32]1[C:31]([CH3:38])=[N:30][C:29]2[N:34]([N:35]=[C:27]3[CH2:26][N:25]([C:23]([C:17]4[CH:18]=[CH:19][C:20]([F:22])=[CH:21][C:16]=4[O:15][C@@H:12]4[CH2:13][CH2:14][NH:9][C@@H:10]([C:40]([F:41])([F:43])[F:42])[CH2:11]4)=[O:24])[CH2:39][C:28]3=2)[C:33]=1[CH3:36]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 131736563HCID 131736563, compound

Product 1

HCID 89662771HCID 89662771, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A 4M solution of HCl in 1,4-dioxane (0.47 mL; 1.87 mmol; 10 eq.) was added to a solution of trans-4-[2-(6-chloro-5,7-dimethyl-1H,3H-2,4,7a,8-tetraaza-cyclopenta[a]indene-2-carbonyl)-5-fluoro-phenoxy]-2-trifluoromethyl-piperidine-1-carboxylic acid tert-butyl ester (115 mg; 0.19 mmol; 1 eq.) in 1,4-dioxane (5 mL) and the reaction mixture was stirred at room temperature for 16 hours. 5M NaOH was added and the mixture extracted with DCM (3×). The combined organics were washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in ACN/water and freeze-dried to afford the title compound (34 mg, 35%) as a yellow solid. 1H NMR (CDCl3) δ 7.45-7.29 (m, 1H), 6.91-6.74 (m, 1H), 6.74-6.60 (m, 1H), 5.12-4.91 (m, 2H), 4.84-4.53 (m, 3H), 3.56-3.29 (m, 1H), 3.07-2.79 (m, 5H), 2.78-2.55 (m, 3H), 2.22-1.99 (m, 1H), 1.99-1.86 (m, 1H), 1.86-1.56 (m, 3H). HPLC (max plot) 92.5%, Rt 3.10 min. UPLC/MS: (MS+) 512.3 ([M+H]+).

Workup

  1. extractionthe mixture extracted with DCM (3×)
  2. washThe combined organics were washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in ACN/water
  6. customfreeze-dried

Sources & evidence

ORD record
ord-b75698c595814189bc44064b7ee22b18
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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