Hydrochloric Acid → HCID 131736557, compound

HRID 1479093Notes

Reaction equation

HRID 1479093 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=2[C:22]([N:24]2[CH2:38][C:27]3=[C:28]4[N:33]([N:34]=[C:26]3[CH2:25]2)[C:32]([CH3:35])=[C:31]([Cl:36])[C:30]([CH3:37])=[N:29]4)=[O:23])[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:39].O1CCOCC1>O.[OH-].[Na+].C(Cl)Cl.CCOCC>[ClH:36].[ClH:39].[Cl:36][C:31]1[C:30]([CH3:37])=[N:29][C:28]2[N:33]([N:34]=[C:26]3[CH2:25][N:24]([C:22]([C:16]4[CH:17]=[CH:18][C:19]([F:21])=[CH:20][C:15]=4[CH2:14][N:11]4[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)=[O:23])[CH2:38][C:27]3=2)[C:32]=1[CH3:35]

Participants

8

Reactant 3

HCID 313Hydrochloric Acid2×HCID 312751,4-DioxaneHCID 122512306HCID 122512306, compound

Product 1

HCID 131736557HCID 131736557, compoundYield 32%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

4-[2-(6-chloro-5,7-dimethyl-1H,3H-2,4,7a,8-tetraaza-cyclopenta[a]indene-2-carbonyl)-5-fluoro-benzyl]-piperazine-1-carboxylic acid tert-butyl ester (133 mg, 0.21 mmol) was added into a mixture of a 4N solution of HCl in dioxane (2 mL, 8.0 mmol) and water (0.4 mL). After 1 hour of stirring at RT, the reaction mixture was diluted with a 1N aqueous solution of NaOH (15 mL) and extracted with DCM (3×25 mL). The organic layers were combined, dried (Na2SO4) and concentrated under vacuum. After purification by flash chromatography (silica, DCM/EtOH/28% aqueous ammonia), the parent compound was obtained as a white solid. The solid was dissolved in DCM (2 ml), then a 2N solution of HCl in Et2O (0.5 mL) was added, followed by Et2O (2 mL). The precipitate was filtered off, washed with Et2O (3×) and dried under vacuum to give the title compound as a white powder (34 mg, 32%). 1H NMR (D2O) δ 7.76-7.67 (m, 1H), 7.47-7.34 (m, 2H), 5.01 (s, 1H), 4.98 (s, 1H), 4.72 (s, 1H), 4.67 (s, 1H), 4.15 (s, 2H), 3.40-3.21 (m, 8H), 2.80 (s, 1.5H), 2.76 (s, 1.5H), 2.63 (s, 1.5H), 2.57 (s, 1.5H). HPLC (max plot) 99.9%, Rt 2.39 min. UPLC/MS: (MS+) 443.4 ([M+H]+), (MS−) 441.4 ([M−H]−).

Workup

  1. extractionextracted with DCM (3×25 mL)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated under vacuum
  4. customAfter purification by flash chromatography (silica, DCM/EtOH/28% aqueous ammonia)
  5. customthe parent compound was obtained as a white solid
  6. filtrationThe precipitate was filtered off
  7. washwashed with Et2O (3×)
  8. customdried under vacuum

Sources & evidence

ORD record
ord-a5666cca5d694a3ab502fe1ff0e2c889
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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