Diisopropylethylamine → 2-amino-N-(2-hydroxy-4-methoxy-phenyl)-5-[1-(1-methyl-4-piperidyl)pyrazol-4-yl]pyridine-3-carboxamide

HRID 908414Notes

Reaction equation

HRID 908414 reaction equation
Cl.[NH2:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[OH:11].C(N(C(C)C)C(C)C)C.OC1C=CC=C[N+]=1[O-].[NH2:29][C:30]1[C:35]([C:36](O)=[O:37])=[CH:34][C:33]([C:39]2[CH:40]=[N:41][N:42]([CH:44]3[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]3)[CH:43]=2)=[CH:32][N:31]=1.Cl.C(N=C=NCCCN(C)C)C>CN(C=O)C>[NH2:29][C:30]1[C:35]([C:36]([NH:2][C:3]2[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=2[OH:11])=[O:37])=[CH:34][C:33]([C:39]2[CH:40]=[N:41][N:42]([CH:44]3[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]3)[CH:43]=2)=[CH:32][N:31]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 122101842-Amino-5-methoxyphenol HydrochlorideHCID 673882572-Amino-5-[1-(1-methyl-4-piperidyl)pyrazol-4-yl]pyridine-3-carboxylic acidHCID 178526252HCID 178526252, compound

Product 1

HCID 673889752-amino-N-(2-hydroxy-4-methoxy-phenyl)-5-[1-(1-methyl-4-piperidyl)pyrazol-4-yl]pyridine-3-carboxamideYield 45.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

2-amino-5-methoxy-phenol hydrochloride (210 mg), N-ethyl-N-isopropyl-propan-2-amine (0.208 ml) and 2-hydroxypyridine-1-oxide (221 mg) were added to a stirred solution of 2-amino-5-[1-(1-methyl-4-piperidyl)pyrazol-4-yl]pyridine-3-carboxylic acid (300 mg) dissolved in DMF (5 ml) under nitrogen. 3-(ethyliminomethyleneamino)-N,N-dimethyl-propan-1-amine hydrochloride (382 mg) was added portionwise to this mixture and the resulting solution was stirred at 25° C. for 48 hours. The reaction mixture was purified by preparative HPLC using a Waters X-Terra reverse-phase column and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford 2-amino-N-(2-hydroxy-4-methoxy-phenyl)-5-[1-(1-methyl-4-piperidyl)pyrazol-4-yl]pyridine-3-carboxamide (190 mg). NMR Spectrum: (DMSOd6) 1.88-2.10 (m, 6H), 2.20 (s, 3H), 2.82-2.90 (m, 2H), 3.71 (s, 3H), 4.06-4.15 (m, 1H), 6.42 (dd, 1H), 6.49 (d, 1H), 6.99 (bs, 2H), 7.26 (d, 1H), 7.85 (s, 1H), 8.16 (s, 1H), 8.30 (d, 1H), 8.39 (d, 1H), 9.51 (bs, 1H), 9.58 (bs, 1H) Mass spectrum: M+H+ 423

Workup

  1. customThe reaction mixture was purified by preparative HPLC
  2. additionThe fractions containing the desired compound
  3. customwere evaporated to dryness

Sources & evidence

ORD record
ord-9cfdc1b1e4f34c5c84ef1410c5e79c5e
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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