Trifluoroacetic acid → HCID 89662827, compound

HRID 1479091Notes

Reaction equation

HRID 1479091 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([O: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])[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[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[O:14][C@H:10]4[CH2:11][CH2:12][CH2:13][NH:8][CH2:9]4)=[O:23])[CH2:38][C:27]3=2)[C:32]=1[CH3:35]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 122512282HCID 122512282, compound

Product 1

HCID 89662827HCID 89662827, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (S)-3-[2-(6-chloro-5,7-dimethyl-1H,3H-2,4,7a,8-tetraaza-cyclopenta[a]indene-2-carbonyl)-5-fluoro-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester (288 mg; 0.53 mmol; 1 eq.) and TFA (3 mL) in DCM (3 mL) was stirred at room temperature for 1 hour then concentrated in vacuo. The residue was taken up in water, the pH made basic with 5M NaOH extracted with DCM (2×). The combined organic layer was dried over magnesium sulfate and concentrated in vacuo. The resulting solid was triturated in water and filtered off to afford the title compound (82 mg, 35%) as an off-white solid. 1H NMR (CDCl3) δ 7.36-7.29 (m, 1H), 6.78-6.68 (m, 2H), 5.01-4.99 (m, 2H), 4.66 (s, 2H), 4.29-0.23 (m, 1H), 3.13-3.06 (m, 1H), 2.91 (s, 2H), 2.86 (s, 1H), 2.84-2.75 (m, 2H), 2.71-2.65 (m, 2H), 2.62 (s, 2H), 2.03-1.91 (m, 1H), 1.78-1.56 (m, 3H), 1.51-1.36 (m, 1H). HPLC (max plot) 98.7%, Rt 2.82 min. UPLC/MS: (MS+) 444.4 ([M+H]+).

Workup

  1. concentrationthen concentrated in vacuo
  2. extractionextracted with DCM (2×)
  3. dry with materialThe combined organic layer 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-7c0965f8b34a45feac770c40b130db4b
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

Loading…