Trifluoroacetic acid → Lanraplenib

HRID 928685Notes

Reaction equation

HRID 928685 reaction equation
C(OC([N:8](C(OC(C)(C)C)=O)[C:9]1[N:14]=[C:13]([C:15]2[N:16]=[C:17]([N:24]([C:32]3[CH:37]=[CH:36][C:35]([N:38]4[CH2:43][CH2:42][N:41]([CH:44]5[CH2:47][O:46][CH2:45]5)[CH2:40][CH2:39]4)=[CH:34][CH:33]=3)C(=O)OC(C)(C)C)[C:18]3[N:19]([CH:21]=[CH:22][N:23]=3)[CH:20]=2)[CH:12]=[N:11][CH:10]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[NH2:8][C:9]1[N:14]=[C:13]([C:15]2[N:16]=[C:17]([NH:24][C:32]3[CH:33]=[CH:34][C:35]([N:38]4[CH2:43][CH2:42][N:41]([CH:44]5[CH2:47][O:46][CH2:45]5)[CH2:40][CH2:39]4)=[CH:36][CH:37]=3)[C:18]3[N:19]([CH:21]=[CH:22][N:23]=3)[CH:20]=2)[CH:12]=[N:11][CH:10]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 118185258tert-Butyl (6-(6-(bis(tert-butoxycarbonyl)amino)pyrazin-2-yl)imidazo[1,2-a]pyrazin-8-yl)(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)carbamate

Product 1

HCID 118161062Lanraplenib

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (6-(6-(bis(tert-butoxycarbonyl)amino)pyrazin-2-yl)imidazo[1,2-a]pyrazin-8-yl)(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)carbamate XVI (200 mg, 0.269 mmol) in DCM (2 ml) was added TFA (0.5 ml, 6.578 mmol). The reaction was stirred at rt for 16 h, saturated sodium bicarbonate was added, extracted with EtOAC and purified on silica gel, eluted with 5% MeOH/EtOAc, 20% MeOH/EtOAc. The desired fractions were combined and concentrated to provide the title compound 2. LCMS-ESI+ (m/z): [M+H]+: 444.2. 1H NMR (300 MHz d6-DMSO) δ: 9.5 (s, 1H), 8.588 (s, 1H), 8.47 (s, 1H), 8.12 (d, 1H), 7.95-7.92 (d, 2H), 7.88 (s, 1H), 7.62 (s, 1H), 6.99-6.96 (d, 2H), 6.46 (s, 2H), 4.57-4.53 (m, 2H), 4.48-4.44 (m, 2H), 3.43 (m, 1H), 3.15-3.12 (m, 4H), 2.41-2.38 (m, 4H).

Workup

  1. extractionextracted with EtOAC
  2. custompurified on silica gel
  3. washeluted with 5% MeOH/EtOAc, 20% MeOH/EtOAc
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-d96cb54918e3419bb1e2d6524682fa07
Source dataset
uspto-grants-2016_03
Patent number
US09290505B2

Reaction notes

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