Toluene → HCID 25261178, compound

HRID 1966226Notes

Reaction equation

HRID 1966226 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH2:10][O:11][CH3:12])=[CH:4][N:3]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.[CH3:59][N:60]1[CH:64]=[CH:63][C:62]([NH2:65])=[N:61]1.C1(C)C=CC=CC=1>C(OCC)(=O)C>[CH3:12][O:11][CH2:10][CH2:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([NH:65][C:62]2[CH:63]=[CH:64][N:60]([CH3:59])[N:61]=2)=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 1372541-Methyl-3-aminopyrazoleHCID 634876Binap, (A+-)-HCID 86644604HCID 86644604, compound

Product 1

HCID 25261178HCID 25261178, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

2-Bromo-5-(2-methoxy-ethoxy)-pyridine (0.42 mmol), sodium-tert.-butylate (1.4 eq.), tris-(dibenzylidene-aceton)-dipalladium (0.1 eq.), BINAP [=2,2′-bis(diphenylphosphino)-1,1′-binaphthyl] (0.1 eq.) and 1-methyl-1H-pyrazole-3-amine (1.4 eq.) are filled under nitrogen in a microwave reaction vessel. Degassed toluene (45 eq.) is added. The reaction suspension is heated for 100 min to 120° C. and for 30 min to 150° C. Ethyl acetate is added to the reaction suspension and filtrated over celite. The solvent of the filtrate is removed in vacuo. [5-(2-Methoxy-ethoxy)-pyridine-2-yl]-(1-methyl-1H-pyrazole-3-yl)-amine (“A22”) is obtained after reversed phase column chromatography (Water/acetonitrile+0.1% TFA) as yellow oil in a yield of 35%: HPLC (method C): 1.16 min; LC-MS (method A): 0.43 min, 249.15 (M+H+); 1H-NMR (DMSO-d6, 500 MHz): δ [ppm] 10.803 (s, 1H), 7.900 (d, 1H, J=2.8 Hz), 7.802 (dd, 1H, J=2.8 Hz, J=9.4 Hz), 7.739 (d, 1H, J=2.3 Hz), 7.314 (d, 1H, J=9.4 Hz), 6.103 (d, 1H, J=2.3 Hz), 4.149-4.131 (m, 2H), 3.861 (s, 3H), 3.688-3.670 (m, 2H), 3.323 (s, 3H).

Workup

  1. temperatureThe reaction suspension is heated for 100 min to 120° C. and for 30 min to 150° C
  2. filtrationfiltrated over celite
  3. customThe solvent of the filtrate is removed in vacuo

Sources & evidence

ORD record
ord-5c8275783df44127afd0f744988d5de0
Source dataset
uspto-grants-2013_04
Patent number
US08420642B2

Reaction notes

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