Trifluoroacetic acid → 2-(2-Isopropyl-5-methoxymethyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoroacetate salt

HRID 1498382Notes

Reaction equation

HRID 1498382 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:38]=[CH:37][C:17]3[C:18]4[N:22]([CH2:23][CH2:24][O:25][C:16]=3[CH:15]=2)[CH:21]=[C:20]([C:26]2[N:27]([CH:34]([CH3:36])[CH3:35])[N:28]=[C:29]([CH2:31][O:32][CH3:33])[N:30]=2)[N:19]=4)[CH2:10][CH2:9]1)=O)(C)(C)C.[F:39][C:40]([F:45])([F:44])[C:41]([OH:43])=[O:42]>C(Cl)Cl>[F:39][C:40]([F:45])([F:44])[C:41]([OH:43])=[O:42].[CH:34]([N:27]1[C:26]([C:20]2[N:19]=[C:18]3[N:22]([CH2:23][CH2:24][O:25][C:16]4[CH:15]=[C:14]([CH:11]5[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]5)[CH:38]=[CH:37][C:17]=43)[CH:21]=2)=[N:30][C:29]([CH2:31][O:32][CH3:33])=[N:28]1)([CH3:36])[CH3:35]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 582048494-[2(2-Isopropyl-5-methoxymethyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 670506872-(2-Isopropyl-5-methoxymethyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoroacetate salt

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-[2-(2-isopropyl-5-methoxymethyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl]-piperidine-1-carboxylic acid tert-butyl ester (158 mg, 0.30 mmol) in DCM (1.5 mL) was added trifluoroacetic acid (1.5 mL, 20.2 mmol) and the reaction mixture stirred at RT for 30 min. The reaction mixture was concentrated in vacuo and the residue azeotroped with ether. The resultant oil was triturated with diethyl ether to give 2-(2-Isopropyl-5-methoxymethyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoroacetate salt as a solid which was collected by filtration (103 mg, 64%). LCMS RT=3.03 min, [M+H]+=423. 1H NMR 400 MHz (DMSO-d) δ: 8.56 (1 H, s), 8.33 (1 H, d, J=8.33 Hz), 7.90 (1 H, s), 7.00 (1 H, dd, J=8.38, 1.78 Hz), 6.85 (1 H, d, J=1.73 Hz), 5.81-5.80 (1 H, m), 4.46 (4 H, d, J=2.51 Hz), 4.33 (2 H, s), 3.34 (2 H, d, J=12.58 Hz), 3.27 (3 H, s), 2.98-2.95 (2 H, m), 2.82 (1 H, t, J=11.91 Hz), 1.93 (2 H, d, J=13.66 Hz), 1.75 (2 H, t, J=12.95 Hz), 1.44 (6 H, d, J=6.60 Hz)

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue azeotroped with ether
  3. customThe resultant oil was triturated with diethyl ether

Sources & evidence

ORD record
ord-0ecbfd0a36214a689ffa890db894baff
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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