Triethylamine → N-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-2-chloro-5-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

HRID 2241387Notes

Reaction equation

HRID 2241387 reaction equation
[CH3:1][O:2][C:3]1[CH:36]=[CH:35][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[C:22]([Cl:24])[C:21]([NH2:25])=[CH:20][C:19]=4[F:26])=[C:11]3[C:10]([NH:27][CH:28]3[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]3)=[N:9]2)=[CH:5][CH:4]=1.[F:37][C:38]1[CH:43]=[CH:42][C:41]([N:44]2[C:49](=[O:50])[C:48]([C:51](O)=[O:52])=[CH:47][CH:46]=[N:45]2)=[CH:40][CH:39]=1.C(N(CC)CC)C.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[C:19]([F:26])=[CH:20][C:21]([NH:25][C:51]([C:48]5[C:49](=[O:50])[N:44]([C:41]6[CH:42]=[CH:43][C:38]([F:37])=[CH:39][CH:40]=6)[N:45]=[CH:46][CH:47]=5)=[O:52])=[C:22]([Cl:24])[CH:23]=4)=[C:11]3[C:10]([NH:27][CH:28]3[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]3)=[N:9]2)=[CH:35][CH:36]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 667671712-(4-Fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acidHCID 685163031-(4-methoxybenzyl)-4-(4-amino-5-chloro-2-fluorophenoxy)-N-(1-methylpiperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine

Product 1

HCID 68515015N-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-2-chloro-5-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamideYield 54.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of 1-(4-methoxybenzyl)-4-(4-amino-5-chloro-2-fluorophenoxy)-N-(1-methylpiperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (130 mg, 0.254 mmol) in CH2Cl2 (1 mL) was added into a solution of 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (119 mg, 0.509 mmol, obtained from Example 19 Step C), triethylamine (0.213 ml, 1.53 mmol), EDCI (293 mg, 1.53 mmol) and HOBT (206 mg, 1.53 mmol) in CH2Cl2 (2 mL). The reaction mixture was stirred for 12 hours at ambient temperature. The reaction was diluted with CH2Cl2 and washed with saturated aqueous NaHCO3 and brine. The organic layer obtained was dried with Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (5% MeOH in CH2Cl2) to afford the product (100 mg, 54.1% yield) as a yellow solid. LRMS (APCI pos) m/e 727.2 (M+H).

Workup

  1. washwashed with saturated aqueous NaHCO3 and brine
  2. customThe organic layer obtained
  3. dry with materialwas dried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography (5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-d1af4afcf579474d9072b6f0adcf72a1
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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