Trifluoroacetic acid → 2-(2-ethylbenzoimidazol-1-yl)-8-(3-fluoroazetidin-3-yl)-9-methyl-6-morpholin-4-yl-9H-purine

HRID 1946186Notes

Reaction equation

HRID 1946186 reaction equation
C(OC([N:8]1[CH2:11][C:10]([C:13]2[N:14]([CH3:39])[C:15]3[C:20]([N:21]=2)=[C:19]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[N:18]=[C:17]([N:28]2[C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=4[N:30]=[C:29]2[CH2:37][CH3:38])[N:16]=3)([F:12])[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:37]([C:29]1[N:28]([C:17]2[N:16]=[C:15]3[C:20]([N:21]=[C:13]([C:10]4([F:12])[CH2:11][NH:8][CH2:9]4)[N:14]3[CH3:39])=[C:19]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[N:18]=2)[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[N:30]=1)[CH3:38]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 596054193-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-fluoroazetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 596055312-(2-ethylbenzoimidazol-1-yl)-8-(3-fluoroazetidin-3-yl)-9-methyl-6-morpholin-4-yl-9H-purineYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-fluoroazetidine-1-carboxylic acid tert-butyl ester (235 mg, 0.44 mmol) in DCM (10 mL) was added TFA (2 mL) and the resulting mixture was allowed to stir at r.t. for 3.5 h. The reaction mixture was concentrated in vacuo and the resulting residue was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH/DCM and the product eluted with 2M NH3/MeOH. The resulting residue was triturated with Et2O and the resulting solid dried in vacuo affording 834 (185 mg, 97%). LCMS (method I): RT 2.50 min, [M+H]+ 437.3. 1H NMR (DMSO, 400 MHz): δ 8.06-8.05 (1 H, m), 7.64-7.63 (1 H, m), 7.28-7.24 (2 H, m), 4.60-4.10 (4 H, brd s), 4.26 (2 H, dd, J=19.18, 10.17 Hz), 4.01 (2 H, dd, J=22.47, 10.23 Hz), 3.80 (4 H, t, J=4.63 Hz), 3.74-3.73 (3 H, m), 3.28-3.27 (2 H, m), 1.34 (3 H, t, J=7.43 Hz)

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. washwas washed with MeOH/DCM
  3. washthe product eluted with 2M NH3/MeOH
  4. customThe resulting residue was triturated with Et2O
  5. customthe resulting solid dried in vacuo

Sources & evidence

ORD record
ord-c681151c6995462685755555444dd2e9
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

Loading…