Triethylamine → N-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxoazepane-3-carboxamide

HRID 2241380Notes

Reaction equation

HRID 2241380 reaction equation
CCN=C=NCCCN(C)C.[F:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]2[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]([C:26]([OH:28])=O)[C:20]2=[O:29])=[CH:15][CH:14]=1.C1C=CC2N(O)N=NC=2C=1.[NH2:40][C:41]1[CH:73]=[CH:72][C:44]([O:45][C:46]2[CH:51]=[CH:50][N:49]=[C:48]3[N:52]([CH2:63][C:64]4[CH:69]=[CH:68][C:67]([O:70][CH3:71])=[CH:66][CH:65]=4)[N:53]=[C:54]([NH:55][CH:56]4[CH2:61][CH2:60][N:59]([CH3:62])[CH2:58][CH2:57]4)[C:47]=23)=[C:43]([F:74])[CH:42]=1.C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O>[CH3:71][O:70][C:67]1[CH:66]=[CH:65][C:64]([CH2:63][N:52]2[C:48]3=[N:49][CH:50]=[CH:51][C:46]([O:45][C:44]4[CH:72]=[CH:73][C:41]([NH:40][C:26]([CH:21]5[CH2:22][CH2:23][CH2:24][CH2:25][N:19]([C:16]6[CH:15]=[CH:14][C:13]([F:12])=[CH:18][CH:17]=6)[C:20]5=[O:29])=[O:28])=[CH:42][C:43]=4[F:74])=[C:47]3[C:54]([NH:55][CH:56]3[CH2:61][CH2:60][N:59]([CH3:62])[CH2:58][CH2:57]3)=[N:53]2)=[CH:69][CH:68]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 685156951-(4-Fluorophenyl)-2-oxoazepane-3-carboxylic acidHCID 685163724-(4-amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-N-(1-methylpiperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine

Product 1

HCID 68512277N-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxoazepane-3-carboxamideYield 67.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

EDCI (48 mg, 0.25 mmol) was added to a mixture of the 1-(4-fluorophenyl)-2-oxoazepane-3-carboxylic acid (21 mg, 0.084 mmol) and HOBT (34 mg, 0.25 mmol) in DMF (0.5 mL) at ambient temperature, and the reaction mixture was stirred for 10 minutes at ambient temperature. 1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-N-(1-methylpiperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (20 mg, 0.042 mmol, obtained from Example 101, Step A) and triethylamine (0.035 ml, 0.25 mmol) were added. The resulting mixture was stirred for 12 hours at ambient temperature. The reaction mixture was diluted with EtOAc. The organic layer washed with 10% aqueous LiCl, dried over Na2SO4, and concentrated. The residue was purified by flash column chromatography (5% MeOH in CH2Cl2) to afford the product (20 mg, 67% yield) as a white solid. LRMS (APCI pos) m/e 710.3 (M+1).

Workup

  1. stirringThe resulting mixture was stirred for 12 hours at ambient temperature
  2. washThe organic layer washed with 10% aqueous LiCl
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography (5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-d78706c953784ef6a4b23b4d7350a87d
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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