1,2-Dimethoxyethane → 1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(2-(4-methylpiperazin-1-yl)pyrimidin-5-yl)-1H-indazole-4-carboxamide

HRID 1476427Notes

Reaction equation

HRID 1476427 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]2[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=2[CH3:26])=[O:17])[C:5]2[CH:6]=[N:7][N:8]([CH:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)[C:9]=2[CH:10]=1.[CH3:29][N:30]1[CH2:35][CH2:34][N:33]([C:36]2[N:41]=[CH:40][C:39](B3OC(C)(C)C(C)(C)O3)=[CH:38][N:37]=2)[CH2:32][CH2:31]1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O>[CH:11]1([N:8]2[C:9]3[CH:10]=[C:2]([C:39]4[CH:38]=[N:37][C:36]([N:33]5[CH2:34][CH2:35][N:30]([CH3:29])[CH2:31][CH2:32]5)=[N:41][CH:40]=4)[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]4[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=4[CH3:26])=[O:17])[C:5]=3[CH:6]=[N:7]2)[CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 164142282-(4-Methylpiperazino)pyrimidine-5-boronic acid pinacol esterHCID 545970746-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1H-indazole-4-carboxamide

Product 1

HCID 545970761-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(2-(4-methylpiperazin-1-yl)pyrimidin-5-yl)-1H-indazole-4-carboxamide

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent

Procedure

To a 2 mL microwave vial were added 6-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (150 mg, 0.338 mmol), 2-(4-methyl-1-piperazinyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (134 mg, 0.440 mmol), Na2CO3 (108 mg, 1.015 mmol), PdCl2(dppf)-CH2Cl2 adduct (27.6 mg, 0.034 mmol), 1,2-Dimethoxyethane (1269 μl) and water (423 μl). The contents were irradiated in a microwave reactor at 150° C. for 30 min. The reaction solution was filtered through a Whatman 0.45 μl Teflon syringless filter device and diluted with DMSO (6 mL). The DMSO solution was purified by HPLC reverse phase chromatography (phenomenex Gemini-NX, 30×100 5μ column, 5-30% acetonitrile/water 0.01% formic acid, 8 min gradient). The fractions containing the desired product were concentrated to dryness using a Genovac HT-4 instrument at 40° C. The title compound was obtained as a pale cream colored foam (28 mg, 14.83% yield). 1H NMR (400 MHz, CHLOROFORM-6) δ 8.62 (s, 2H), 8.39 (s, 1H), 7.99 (t, J=5.56 Hz, 1H), 7.71 (s, 1H), 7.57 (s, 1H), 5.98 (s, 1H), 5.03 (quin, J=7.14 Hz, 1H), 4.66 (d, J=5.81 Hz, 2H), 3.97 (br. s., 4H), 2.64 (br. s., 4H), 2.44 (s, 6H), 2.12-2.25 (m, 7H), 1.89-2.07 (m, 2H), 1.67-1.85 (m, 2H). LCMS (ES) [M+H]+ 541.5.

Workup

  1. customThe contents were irradiated in a microwave reactor at 150° C. for 30 min
  2. filtrationThe reaction solution was filtered through a Whatman 0.45 μl Teflon syringless filter device
  3. additiondiluted with DMSO (6 mL)
  4. customThe DMSO solution was purified by HPLC reverse phase chromatography (phenomenex Gemini-NX, 30×100 5μ column, 5-30% acetonitrile/water 0.01% formic acid, 8 min gradient)
  5. additionThe fractions containing the desired product
  6. concentrationwere concentrated to dryness
  7. customat 40° C

Sources & evidence

ORD record
ord-e4977266c2da4b0ba6a4c0ee2a47796b
Source dataset
uspto-grants-2015_04
Patent number
US09018382B2

Reaction notes

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