Trifluoroacetic acid → HCID 73054870, compound

HRID 1779053Notes

Reaction equation

HRID 1779053 reaction equation
C(O)(C(F)(F)F)=O.[NH2:8][C:9](=[O:50])[CH2:10][C:11]1[CH:48]=[CH:47][C:46]([CH3:49])=[CH:45][C:12]=1[CH2:13][CH2:14][C:15]1[C:20]([C:21]([F:24])([F:23])[F:22])=[CH:19][N:18]=[C:17]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([CH:32]3[CH2:37][CH2:36][N:35](C(OC(C)(C)C)=O)[CH2:34][CH2:33]3)=[CH:28][CH:27]=2)[N:16]=1>C(Cl)Cl.C1CCCCC1>[CH3:49][C:46]1[CH:47]=[CH:48][C:11]([CH2:10][C:9]([NH2:8])=[O:50])=[C:12]([CH2:13][CH2:14][C:15]2[C:20]([C:21]([F:24])([F:22])[F:23])=[CH:19][N:18]=[C:17]([NH:25][C:26]3[CH:27]=[CH:28][C:29]([CH:32]4[CH2:33][CH2:34][NH:35][CH2:36][CH2:37]4)=[CH:30][CH:31]=3)[N:16]=2)[CH:45]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86712697HCID 86712697, compound

Product 1

HCID 73054870HCID 73054870, compoundYield 96.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8078CyclohexaneSolvent

Procedure

TFA (0.5 mL) was added to a solution of tert-butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)-5-methylphenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A90) (0.106 g, 0.177 mmol) in DCM (5 mL) and the resulting mixture stirred at room temperature for 17 hours. The solvent was removed in vacuo and the residue partitioned between EtOAc (20 mL) and 2 M aqueous NaOH (20 mL). The aqueous layer was extracted with EtOAc (2×10 mL) and the combined organic layers washed with water (20 mL), brine (20 mL) and dried over MgSO4. The volatiles were removed in vacuo to give a solid which was suspended in DCM and cyclohexane. The resulting suspension was filtered to give the title compound 21 as a white solid (0.085 g, 96%); 1H NMR (400 MHz, d4-MeOH) δ 8.54 (s, 1H), 7.62 (d, J=8.6 Hz, 2H), 7.22 (d, J=8.5 Hz, 2H), 7.14 (d, J=7.7 Hz, 1H), 7.06-6.98 (m, 2H), 3.62 (s, 2H), 3.28-3.21 (m, 2H), 3.15-3.08 (m, 2H), 3.08-3.01 (m, 2H), 2.86 (td, J=12.6, 2.6 Hz, 2H), 2.78-2.67 (m, 1H), 2.26 (s, 3H), 1.91 (d, J=12.0 Hz, 2H), 1.74 (qd, J=12.9, 4.0 Hz, 2H). LCMS-A: rt 4.94 min; m/z 498.3 [M+H]+.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue partitioned between EtOAc (20 mL) and 2 M aqueous NaOH (20 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  4. washthe combined organic layers washed with water (20 mL), brine (20 mL)
  5. dry with materialdried over MgSO4
  6. customThe volatiles were removed in vacuo
  7. customto give a solid which
  8. filtrationThe resulting suspension was filtered

Sources & evidence

ORD record
ord-db6b111cb4f34063a7bc7f43ea2cfcd2
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

Loading…