Diisopropylethylamine → {1-[6-(4-Benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-4-phenyl-piperidin-4-yl}-carbamic acid tert-butyl ester

HRID 2360698Notes

Reaction equation

HRID 2360698 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[C:17]([C:31](O)=[O:32])[C:18]3[C:23]([CH3:24])=[N:22][N:21]([CH:25]4[CH2:30][CH2:29][CH2:28][CH2:27][O:26]4)[C:19]=3[N:20]=2)=[C:11]([F:34])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:35]([O:39][C:40](=[O:54])[NH:41][C:42]1([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1)([CH3:38])([CH3:37])[CH3:36].CCN(C(C)C)C(C)C>ClCCl>[C:35]([O:39][C:40](=[O:54])[NH:41][C:42]1([C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH2:43][CH2:44][N:45]([C:31]([C:17]2[C:18]3[C:23]([CH3:24])=[N:22][N:21]([CH:25]4[CH2:30][CH2:29][CH2:28][CH2:27][O:26]4)[C:19]=3[N:20]=[C:15]([C:12]3[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:10][C:11]=3[F:34])[CH:16]=2)=[O:32])[CH2:46][CH2:47]1)([CH3:38])([CH3:36])[CH3:37]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 9903704tert-butyl N-(4-phenylpiperidin-4-yl)carbamateHCID 866803216-(4-benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid

Product 1

HCID 86680320{1-[6-(4-Benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-4-phenyl-piperidin-4-yl}-carbamic acid tert-butyl esterYield 16%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 6-(4-benzyloxy-2-fluoro-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (384 mg), (4-phenylpiperidin-4-yl)-carbamic acid tert-butyl ester (230 mg), DIPEA (427 μL) and BEP (456 mg) in dichloromethane (10 mL) was stirred at r.t. for 5 d. The solvent was distilled off in vacuo, the residue was re-dissolved in MTBE/ethyl acetate (v/v=1/1, 40 mL) and washed once with water, twice with saturated sodium bicarbonate solution, once with 1N sodium hydroxide solution and with brine. After evaporation of the solvents, the residue was purified by flash chromatography (silica, heptane/ethyl acetate gradient) giving 95 mg (16%) of the title compound.

Workup

  1. distillationThe solvent was distilled off in vacuo
  2. dissolutionthe residue was re-dissolved in MTBE/ethyl acetate (v/v=1/1, 40 mL)
  3. washwashed once with water, twice with saturated sodium bicarbonate solution, once with 1N sodium hydroxide solution and with brine
  4. customAfter evaporation of the solvents
  5. customthe residue was purified by flash chromatography (silica, heptane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-a3ff4da7ecbe49d0bbbc6e144f1e89cd
Source dataset
uspto-grants-2014_04
Patent number
US08686150B2

Reaction notes

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