Diisopropylethylamine → Methyl 2-(5-(2-((3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)methyl)-4-fluorophenoxy)-1H-indazol-1-yl)acetate

HRID 1666764Notes

Reaction equation

HRID 1666764 reaction equation
Cl.Cl.[NH2:3][CH2:4][C:5]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:6]=1[O:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([CH2:17][C:18]([O:20][CH3:21])=[O:19])[N:12]=[CH:11]2.ClC(Cl)(Cl)C[O:30][C:31](=O)[NH:32][C:33]1[N:37]([C:38]2[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=2)[N:36]=[C:35]([C:45]([CH3:48])([CH3:47])[CH3:46])[CH:34]=1.C(N(C(C)C)CC)(C)C>CC(N(C)C)=O>[C:45]([C:35]1[CH:34]=[C:33]([NH:32][C:31](=[O:30])[NH:3][CH2:4][C:5]2[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:6]=2[O:7][C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH2:17][C:18]([O:20][CH3:21])=[O:19])[N:12]=[CH:11]3)[N:37]([C:38]2[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=2)[N:36]=1)([CH3:48])([CH3:47])[CH3:46]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 66671265methyl 2-(5-(2-(aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)acetate dihydrochloride

Product 1

HCID 57552299Methyl 2-(5-(2-((3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)methyl)-4-fluorophenoxy)-1H-indazol-1-yl)acetateYield 89%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of methyl 2-(5-(2-(aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)acetate dihydrochloride (17.5 g, 43.51 mmol) in dimethylacetamide (0.5M, 88 mL) was treated with 2,2,2-trichloroethyl-3-tert-butyl-1-p-tolyl-1H-pyrazol-5-ylcarbamate (17.96 g, 44.38 mmol), followed by diisopropylethylamine (30.3 mL, 174 mmol) at room temperature. The mixture was heated at 80° C. overnight. The mixture was concentrated in vacuo and the residue distributed between EtOAc and saturated aqueous NH4Cl. The organic layer was separated and washed with brine, filtered through 1PS paper, evaporated in vacuo to a brown foam. The foam was triturated in ether, and the precipitated solids were collected by filtration to provide 22.55 g (89%) of the desired compound. MS (APCI+) m/z 585 (M+1) detected. 1H NMR (400 MHz, DMSO-d6) δ 8.3 (s, 1H), 8.07 (s, 1H), 7.68 (d, 1H, J=8.9 Hz), 6.85-7.37 (m, 8H), 6.24 (s, 1H), 5.4 (s, 2H), 4.28 (d, 2H, J=5.8 Hz), 3.68 (s, 3H), 2.35 (s, 3H), 1.25 (s, 9H).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customThe organic layer was separated
  3. washwashed with brine
  4. filtrationfiltered through 1PS paper
  5. customevaporated in vacuo to a brown foam
  6. customThe foam was triturated in ether
  7. filtrationthe precipitated solids were collected by filtration

Sources & evidence

ORD record
ord-c1b1bd9ad8d4427bbfd52eabad27bcab
Source dataset
uspto-grants-2011_10
Patent number
US08044083B2

Reaction notes

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