Hydrochloric Acid → HCID 90647121, compound

HRID 2200064Notes

Reaction equation

HRID 2200064 reaction equation
[Cl:1]C(Cl)(Cl)CO[C:5](=[O:17])[NH:6][C:7]1[N:8]([CH3:16])[N:9]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:11]=1.[NH2:20][C@@H:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C@H:24]([O:31][C:32]2[CH:33]=[CH:34][C:35]3[N:36]([C:38]([C@H:41]4[N:45]([CH3:46])[CH2:44][C@@H:43]([N:47]([CH3:49])[CH3:48])[CH2:42]4)=[N:39][N:40]=3)[CH:37]=2)[CH2:23][CH2:22]1.CCN(C(C)C)C(C)C.Cl>O1CCOCC1.CC#N>[ClH:1].[C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:20][C@@H:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C@H:24]([O:31][C:32]3[CH:33]=[CH:34][C:35]4[N:36]([C:38]([C@@H:41]5[CH2:42][C@H:43]([N:47]([CH3:49])[CH3:48])[CH2:44][N:45]5[CH3:46])=[N:39][N:40]=4)[CH:37]=3)[CH2:23][CH2:22]2)=[O:17])[N:8]([CH3:16])[N:9]=1)([CH3:13])([CH3:14])[CH3:15]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 594208722,2,2-Trichloroethyl (3-tert-butyl-1-methyl-1H-pyrazol-5-yl)carbamateHCID 117729265HCID 117729265, compound

Product 1

HCID 90647121HCID 90647121, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

(5-Tert-butyl-2-methyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (US2004/0192653, which is incorporated herein by reference in its entirety; 242 mg, 0.74 mmol) was treated with a solution of Intermediate 38d (300 mg, 0.74 mmol) in 1,4-dioxane (5 mL) then DIPEA (185 μL, 1.1 mmol) was added. The mixture was stirred at 50° C. overnight. The mixture was evaporated in vacuo and the residue purified by HPLC (Method 6, 20-40% MeCN in H2O, 0.1% HCO2H over 30 min) to give a colourless glass that was dissolved in MeCN and treated with 1N HCl (550 μL, 1 eq.). The volatiles were evaporated to drieness under reduced pressure affording a colourless glass that upon trituration with ether gave a solid. The solid was collected by filtration, washed with ether and dried at 50° C. in vacuo to give the title compound as an off white solid (346 mg, 74%). LCMS (Method 5): Rt 3.01 min, m/z 586.4 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.20 (9H, s), 1.81-2.15 (5H, m), 2.16-2.24 (2H, bs), 2.42-2.52 (4H, br s, partially obscured by DMSO), 2.74-2.80 (6H, s), 3.45-3.53 (2H, m), 3.56 (3H, s), 3.97-4.06 (1H, m), 4.79-4.88 (1H, m), 5.54 (1H, t, J 4.3 Hz), 6.00 (1H, s), 7.08 (1H, d, J 8.4 Hz), 7.22-7.27 (1H, m), 7.33-7.39 (4H, m), 7.77 (1H, d, J 9.3 Hz), 8.45 (1H, bs), 8.60 (1H, s).

Workup

  1. customThe mixture was evaporated in vacuo
  2. customthe residue purified by HPLC (Method 6, 20-40% MeCN in H2O, 0.1% HCO2H over 30 min)
  3. customto give a colourless glass that
  4. customThe volatiles were evaporated to drieness under reduced pressure
  5. customaffording a colourless glass that upon trituration with ether
  6. customgave a solid
  7. filtrationThe solid was collected by filtration
  8. washwashed with ether
  9. customdried at 50° C. in vacuo

Sources & evidence

ORD record
ord-69ded6f3a1844837a78abdfeb855654a
Source dataset
uspto-grants-2016_06
Patent number
US09359354B2

Reaction notes

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