Cyclopropanemethanamine, N-propyl- → 7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine-3-carboxylic acid cyclopropylmethylpropylamide

HRID 1826962

Reaction equation

HRID 1826962 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[N:10]1[CH2:15][CH2:14][CH2:13][C:12]2=[C:16]([C:20]([OH:22])=O)[N:17]([CH3:19])[N:18]=[C:11]12.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH2:46]([NH:49][CH2:50][CH:51]1[CH2:53][CH2:52]1)[CH2:47][CH3:48]>ClCCl.C(N(CC)CC)C>[CH:51]1([CH2:50][N:49]([CH2:46][CH2:47][CH3:48])[C:20]([C:16]2[N:17]([CH3:19])[N:18]=[C:11]3[C:12]=2[CH2:13][CH2:14][CH2:15][N:10]3[C:3]2[C:4]([CH3:9])=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=2[Cl:1])=[O:22])[CH2:53][CH2:52]1

Participants

7

Reactant 4

HCID 117787Cyclopropanemethanamine, N-propyl-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 221362637-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine-3-carboxylic acid

Product 1

HCID 221362777-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine-3-carboxylic acid cyclopropylmethylpropylamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

7-(2-Chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine-3-carboxylic acid (107.0 mg), 1-hydroxybenzotriazole hydrate (50.3 mg), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (72.5 mg), triethylamine (93 μL), and N-propylcyclopropanemethylamine (49 μL) were combined in 4 mL of dichloromethane and stirred at room temperature over night. The reaction mixture was then partitioned between ethyl acetate and 1M hydrochloric acid. The ethyl acetate solution was washed with aqueous sodium bicarbonate, dried with magnesium sulfate, and concentrated. The crude product was chromatographed on silica gel eluting with an acetone/hexane gradient giving a solid. Recrystallization from hexane provided 75.6 mg of 7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine-3-carboxylic acid cyclopropylmethylpropylamide, mp 120.6–122.0° C.

Workup

  1. customThe reaction mixture was then partitioned between ethyl acetate and 1M hydrochloric acid
  2. washThe ethyl acetate solution was washed with aqueous sodium bicarbonate
  3. dry with materialdried with magnesium sulfate
  4. concentrationconcentrated
  5. customThe crude product was chromatographed on silica gel eluting with an acetone/hexane gradient
  6. customgiving a solid
  7. customRecrystallization from hexane

Sources & evidence

ORD record
ord-fd71b2e27ddc4685a00f6ce555178086
Source dataset
uspto-grants-2006_05
Patent number
US07053103B2

Linked notes

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