Trifluoroacetic acid → HCID 89662743, compound

HRID 1479089Notes

Reaction equation

HRID 1479089 reaction equation
C(OC([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=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])[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=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])[CH2:9]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 89650267HCID 89650267, compound

Product 1

HCID 89662743HCID 89662743, compoundYield 18.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-[2-(6-chloro-5,7-dimethyl-1H,3H-2,4,7a,8-tetraaza-cyclopenta[a]indene-2-carbonyl)-5-fluoro-phenoxy]-azetidine-1-carboxylic acid tert-butyl ester (472 mg; 0.91 mmol; 1 eq.) and TFA (4 mL) in DCM (4 mL) was stirred at room temperature for 1 hour then concentrated in vacuo. The residue was taken up in water, the pH was made basic with 5M NaOH and extracted with DCM (2×). The combined organic phase was dried over magnesium sulfate and concentrated in vacuo. The resulting solid was triturated in water and filtered off to afford the title compound (70 mg, 18%) as a white solid. 1H NMR (CDCl3) δ 7.38-7.31 (m, 1H), 6.80-6.72 (m, 1H), 6.38 (dt, J=10.5, 2.0 Hz, 1H), 5.04-4.96 (m, 3H), 4.65 (s, 2H), 3.93-3.87 (m, 2H), 3.79-3.72 (m, 2H), 2.91 (s, 2H), 2.86 (s, 1H), 2.69 (s, 1H), 2.63 (s, 2H). HPLC (max plot) 94.9%, Rt 2.56 min. UPLC/MS: (MS+) 416.2 ([M+H]+).

Workup

  1. concentrationthen concentrated in vacuo
  2. extractionextracted with DCM (2×)
  3. dry with materialThe combined organic phase was dried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe resulting solid was triturated in water
  6. filtrationfiltered off

Sources & evidence

ORD record
ord-da0ddf3b4d4e44f38e9b9e23e2aa3ad5
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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