Trifluoroacetic acid → 2-Amino-1-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-2-methyl-propan-1-one

HRID 1190672Notes

Reaction equation

HRID 1190672 reaction equation
C(OC(=O)[NH:7][C:8]([CH3:38])([CH3:37])[C:9]([N:11]1[CH2:14][CH:13]([C:15]2[CH:36]=[CH:35][C:18]3[C:19]4[N:20]=[C:21]([C:27]5[N:28]([CH:32]([CH3:34])[CH3:33])[N:29]=[CH:30][N:31]=5)[S:22][C:23]=4[CH2:24][CH2:25][O:26][C:17]=3[CH:16]=2)[CH2:12]1)=[O:10])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][C:8]([CH3:38])([CH3:37])[C:9]([N:11]1[CH2:12][CH:13]([C:15]2[CH:36]=[CH:35][C:18]3[C:19]4[N:20]=[C:21]([C:27]5[N:28]([CH:32]([CH3:34])[CH3:33])[N:29]=[CH:30][N:31]=5)[S:22][C:23]=4[CH2:24][CH2:25][O:26][C:17]=3[CH:16]=2)[CH2:14]1)=[O:10]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67050555(2-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-1,1-dimethyl-2-oxo-ethyl)-carbamic acid tert-butyl ester

Product 1

HCID 582037892-Amino-1-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-2-methyl-propan-1-oneYield 71.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-1,1-dimethyl-2-oxo-ethyl)-carbamic acid tert-butyl ester (203 mg, 0.36 mmol) in DCM (2 mL) was added TFA (2 mL) and the reaction mixture was stirred for 1 hour then concentrated in vacuo. The residual solid was triturated with ether, filtered off and air-dried before being dissolved in DCM. The organic solution was washed (aqueous saturated sodium bicarbonate solution, followed by water and then brine), dried (MgSO4) and concentrated in vacuo. The residue was freeze-dried from MeOH/H2O to give 469 as a white solid (116 mg, 71%). LCMS: RT=8.13 min, [M+H]+=453. 1H NMR δ (ppm) (DMSO-d6): 8.30 (1H, d, J=8.19 Hz), 8.06 (1H, s), 7.18 (1H, dd, J=8.24, 1.86 Hz), 7.00 (1H, d, J=1.82 Hz), 5.82-5.74 (1H, m), 4.79 (1H, s), 4.42 (1H, s), 4.33 (2H, t, J=5.13 Hz), 4.19 (1H, s), 3.77-3.70 (2H, m), 3.39 (2H, t, J=5.02 Hz), 1.74 (2H, s), 1.50 (6H, d, J=6.59 Hz), 1.17 (6H, s)

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe residual solid was triturated with ether
  3. filtrationfiltered off
  4. customair-dried
  5. dissolutionbefore being dissolved in DCM
  6. washThe organic solution was washed (aqueous saturated sodium bicarbonate solution
  7. dry with materialbrine), dried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. dry with materialThe residue was freeze-dried from MeOH/H2O

Sources & evidence

ORD record
ord-eb4920ac0a4d4f23b1b818ccddf709b6
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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