Diisopropylethylamine → 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[2-(1-methyl-1H-indazol-5-yloxy)-pyridin-3-ylmethyl]-urea

HRID 1715564Notes

Reaction equation

HRID 1715564 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([O:11][C:12]3[C:17]([CH2:18][NH2:19])=[CH:16][CH:15]=[CH:14][N:13]=3)=[CH:8][CH:9]=2)[CH:4]=[N:3]1.ClC(Cl)(Cl)C[O:23][C:24](=O)[NH:25][C:26]1[N:27]([C:35]2[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=2)[N:28]=[C:29]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH:30]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[C:31]([C:29]1[CH:30]=[C:26]([NH:25][C:24]([NH:19][CH2:18][C:17]2[C:12]([O:11][C:7]3[CH:6]=[C:5]4[C:10](=[CH:9][CH:8]=3)[N:2]([CH3:1])[N:3]=[CH:4]4)=[N:13][CH:14]=[CH:15][CH:16]=2)=[O:23])[N:27]([C:35]2[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=2)[N:28]=1)([CH3:34])([CH3:32])[CH3:33]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 674103932-[(1-Methyl-1H-indazol-5-yl)oxy]-3-pyridinemethanamine

Product 1

HCID 426418721-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[2-(1-methyl-1H-indazol-5-yloxy)-pyridin-3-ylmethyl]-ureaYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

C-[2-(1-Methyl-1H-indazol-5-yloxy)-pyridin-3-yl]-methylamine (4n) (0.017 g, 0.067 mmol) and (5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (5n) (0.035 g, 0.087 mmol) were placed in a 10 mL reactor vial and dissolved in DMF (5 mL). DIEA (0.058 mL, 0.334 mmol) was added to the reaction mixture and the system heated to 80° C. for 18 hours. The reaction mixture was concentrated under reduced pressure to afford the crude product. The crude material was purified by flash column chromatography using Sep-pak 10 g (35 cc) silica cartridge (50% EtOAc/Hexanes) to furnish the desired product (6n) (0.034 g, 100% yield). 1H NMR (400 mHz, DMSO) δ 8.32 (s, 1H), 8.00 (s, 1H), 7.94 (d, J=4.7 Hz, 1H), 7.65 (d, J=8.6 Hz, 1H), 7.60 (d, J=7.8 Hz, 1H), 7.46 (s, 1H), 7.36 (d, J=7.8 Hz, 2H), 7.29 (d, J=7.8 Hz, 2H), 7.19-7.16 (m, 1H), 7.07-7.03 (m, 2H), 6.26 (s, 1H), 4.37 (d, J=6.3 Hz, 2H), 4.06 (s, 3H), 2.36 (s, 3H), 1.25 (s, 9H); MS (ESI+) m/z 510 (M+H) detected.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto afford the crude product
  3. customThe crude material was purified by flash column chromatography

Sources & evidence

ORD record
ord-44a95bc3e241467c90fc00ee2820172b
Source dataset
uspto-grants-2010_09
Patent number
US07799782B2

Reaction notes

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