1-Hydroxybenzotriazole → HCID 178434421, compound

HRID 336849Notes

Reaction equation

HRID 336849 reaction equation
[C:1]([C:3]1[C:4]([C@@H:21]2[CH2:23][C@H:22]2[C:24](O)=[O:25])=[C:5]2[C:19]([CH3:20])=[N:18][NH:17][C:6]2=[N:7][C:8]=1[C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[F:16])#[N:2].[NH2:27][CH:28]1[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]1.N1(O)C2C=CC=CC=2N=N1>CN(C)C=O.CN(C)C1C=CN=CC=1>[C:1]([C:3]1[C:4]([C@@H:21]2[CH2:23][C@H:22]2[C:24]([NH:27][CH:28]2[CH2:29][CH2:30][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:32][CH2:33]2)=[O:25])=[C:5]2[C:19]([CH3:20])=[N:18][NH:17][C:6]2=[N:7][C:8]=1[C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[F:16])#[N:2]

Participants

6

Reactant 3

HCID 757711-HydroxybenzotriazoleHCID 12682914-Amino-1-Boc-piperidineHCID 178434422HCID 178434422, compound

Product 1

HCID 178434421HCID 178434421, compoundYield 51.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To 200 mg (0.57 mmol) of (1R,2R)-2-(5-cyano-6-(2-fluoro-4-hydroxyphenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-yl)cyclopropane carboxylic acid diluted in 4 ml of anhydrous dimethylformamide are added, at 0° C., 121 mg (0.57 mmol) of tert-butyl 4-aminopiperidine-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 give 158 mg of tert-butyl 4-((1R,2R)-2-(5-cyano-6-(2-fluoro-4-hydroxyphenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)cyclopropanecarboxamido)piperidine-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-58cc6a5b86984257a9f39b5d1e5f00eb
Source dataset
uspto-grants-2014_11
Patent number
US08889711B2

Reaction notes

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