1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 178434423, compound

HRID 336850Notes

Reaction equation

HRID 336850 reaction equation
[C:1]([C:3]1[C:8]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=2[F:16])=[N:7][C:6]2[NH:17][N:18]=[C:19]([CH3:20])[C:5]=2[C:4]=1[C:21](O)=[O:22])#[N:2].[N:24]1([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.CCN=C=NCCCN(C)C.N1(O)C2C=CC=CC=2N=N1>CN(C)C=O.CN(C)C1C=CN=CC=1>[C:1]([C:3]1[C:8]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=2[F:16])=[N:7][C:6]2[NH:17][N:18]=[C:19]([CH3:20])[C:5]=2[C:4]=1[C:21]([N:27]1[CH2:26][CH2:25][N:24]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:29][CH2:28]1)=[O:22])#[N:2]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 143452tert-Butyl piperazine-1-carboxylateHCID 178434424HCID 178434424, compound

Product 1

HCID 178434423HCID 178434423, compoundYield 57.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To 200 mg (0.57 mmol) of 5-cyano-6-(2-fluoro-4-hydroxyphenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid diluted in 4 ml of anhydrous dimethylformamide are added at 0° C. 121 mg (0.57 mmol) of tert-butyl piperazine-1-carboxylate, 76 mg (0.62 mmol) of N,N-dimethylpyridine-4-amine (DMAP), 110 mg (0.62 mmol) of N,N-dimethyl-N-[(methylimino)methylene]propane-1,3-diamine hydrochloride (EDCI) and 84 mg (0.62 mmol) of 1H-benzo[d][1,2,3]triazole-1-ol (HOBT). The reaction mixture is stirred 20 h at room temperature. The solvent is concentrated, water is added and the product extracted several times with ethyl acetate. The organic phases are combined, dried over magnesium sulfate, and concentrated. The residue is purified by chromatography on silica (cyclohexane/ethyl acetate eluent: 5:5 to 3:7) to yield 158 mg of tert-butyl 4-(5-cyano-6-(2-fluoro-4-hydroxyphenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-carbonyl)piperazine-1-carboxylate in the form of a white solid.

Workup

  1. additionare added at 0° C
  2. concentrationThe solvent is concentrated
  3. additionwater is added
  4. extractionthe product extracted several times with ethyl acetate
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue is purified by chromatography on silica (cyclohexane/ethyl acetate eluent: 5:5 to 3:7)

Sources & evidence

ORD record
ord-921403a155f94063854a69a71d69dec4
Source dataset
uspto-grants-2014_11
Patent number
US08889711B2

Reaction notes

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