Dichloromethane → HCID 67050609, compound

HRID 708267Notes

Reaction equation

HRID 708267 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][C:11]([OH:36])([C:14]2[CH:35]=[CH:34][C:17]3[C:18]4[N:19]=[C:20]([C:26]5[N:27]([CH:31]([CH3:33])[CH3:32])[N:28]=[CH:29][N:30]=5)[S:21][C:22]=4[CH2:23][CH2:24][O:25][C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)[Cl:45]>>[ClH:45].[CH:31]([N:27]1[C:26]([C:20]2[S:21][C:22]3[CH2:23][CH2:24][O:25][C:16]4[CH:15]=[C:14]([C:11]5([OH:36])[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]5)[CH:35]=[CH:34][C:17]=4[C:18]=3[N:19]=2)=[N:30][CH:29]=[N:28]1)([CH3:33])[CH3:32]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 582038674-hydroxy-4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 67050609HCID 67050609, compoundYield 51%

Procedure

To a solution of 4-hydroxy-4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidine-1-carboxylic acid tert-butyl ester (20 mg, 39 μmol) in DCM (2 mL) was added TFA (0.5 mL) and the reaction mixture stirred at RT for 3 h. The reaction mixture was concentrated in vacuo and the resultant residue subjected to flash chromatography (Si—NH2, gradient 1-4% MeOH in DCM). The purified product was dissolved in MeOH (5 mL) and HCl (0.5 mL, 3N in MeOH) added. The reaction mixture was concentrated in vacuo and the residue triturated with MeCN to give 517 as a colourless solid (9 mg, 51%). LCMS: RT=2.94 min, [M+H]+=412 [ad823591] 1H NMR 400 MHz (d6-DMSO) δ: 8.38 (1H, d, J=8.2 Hz), 7.97 (1H, s), 7.28 (1H, dd, J=8.2, 1.9 Hz), 7.20 (1H, d, J=1.9 Hz), 5.93 (1H, sept, J=6.6 Hz), 4.37 (2H, t, J=5.0 Hz), 3.49-3.29 (6H, m), 2.29-2.17 (2H, m), 1.98-1.90 (2H, m), 1.59 (6H, d, J=6.6 Hz)

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionThe purified product was dissolved in MeOH (5 mL)
  3. additionHCl (0.5 mL, 3N in MeOH) added
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customthe residue triturated with MeCN

Sources & evidence

ORD record
ord-e07caffc44d04c1c9416cc60cbb12e62
Source dataset
uspto-grants-2015_11
Patent number
US09175009B2

Reaction notes

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