Triethylamine → HCID 54760609, compound

HRID 929996Notes

Reaction equation

HRID 929996 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:19])OC2C=CC=CC=2)[N:7]([CH3:20])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[NH2:23][C:24]1[CH:29]=[CH:28][C:27]([NH:30][C:31](=[O:50])[C:32]2[CH:37]=[CH:36][C:35]([O:38][CH:39]3[CH2:44][C:43]([CH3:46])([CH3:45])[N:42]([CH3:47])[C:41]([CH3:49])([CH3:48])[CH2:40]3)=[CH:34][N:33]=2)=[CH:26][CH:25]=1.C(N(CC)CC)C>CN(C)C1C=CN=CC=1.C1COCC1>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:19])[NH:23][C:24]2[CH:29]=[CH:28][C:27]([NH:30][C:31](=[O:50])[C:32]3[CH:37]=[CH:36][C:35]([O:38][CH:39]4[CH2:44][C:43]([CH3:45])([CH3:46])[N:42]([CH3:47])[C:41]([CH3:49])([CH3:48])[CH2:40]4)=[CH:34][N:33]=3)=[CH:26][CH:25]=2)[N:7]([CH3:20])[N:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 46196890phenyl 3-tert-butyl-1-methyl-1H-pyrazol-5-ylcarbamateHCID 67125891HCID 67125891, compound

Product 1

HCID 54760609HCID 54760609, compoundYield 6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-tert-butyl-1-methyl-1H-pyrazol-5-ylcarbamate from Step 1 of this example (65 mg, 0.24 mmol), N-(4-aminophenyl)-5-(1,2,2,6,6-pentamethylpiperidin-4-yloxy)picolinamide dihydrochloride from Example 49 (90 mg, 0.20 mmol), triethylamine (92 μL, 0.66 mmol), and N,N-dimethylpyridin-4-amine (2 mg, 0.02 mmol) in THF (3 mL) was stirred at rt for 2 d. The solvent was removed under reduced pressure. The crude residue was purified by silica gel flash chromatography, eluting with 9% MeOH/1% NH3 in DCM. The resulting compound was then purified by reverse phase HPLC to afford N-(4-(3-(3-tert-butyl-1-methyl-1H-pyrazol-5-yl)ureido)phenyl)-5-(1,2,2,6,6-pentamethylpiperidin-4-yloxy)picolinamide (7 mg, 6% yield). LCMS (ESI) m/z 562 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 10.32 (s, 1H), 9.76 (br s, 1H), 9.47 (br s, 1H), 8.35-8.34 (d, 1H), 8.11-8.08 (d, 1H), 7.78-7.75 (d, 2H), 7.63-7.59 (d, 1H), 7.47-7.44 (d, 2H), 6.02 (s, 1H), 4.87 (t, 1H), 3.6 (s, 3H), 2.2 (s, 3H), 2.04-1.99 (d, 2H), 1.49-1.42 (t, 2H), 1.21 (s, 9H), 1.13-1.12 (m, 12H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customThe crude residue was purified by silica gel flash chromatography
  3. washeluting with 9% MeOH/1% NH3 in DCM
  4. customThe resulting compound was then purified by reverse phase HPLC

Sources & evidence

ORD record
ord-097b50e8e5d848dba190d374da57397b
Source dataset
uspto-grants-2016_03
Patent number
US09296722B2

Reaction notes

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