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Sodium Carbonate → N2-{4-[4-amino-1-(3-morpholinopropyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide

HRID 2056197
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HRID 2056197 반응식
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH2:12][CH2:13][CH2:14][N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:3]=1.[CH3:21][O:22][C:23]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=[CH:25][C:24]=1[NH:38][C:39]([C:41]1[N:42]([CH3:50])[C:43]2[C:48]([CH:49]=1)=[CH:47][CH:46]=[CH:45][CH:44]=2)=[O:40].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH2:12][CH2:13][CH2:14][N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[N:3]=[C:2]([C:27]3[CH:26]=[CH:25][C:24]([NH:38][C:39]([C:41]4[N:42]([CH3:50])[C:43]5[C:48]([CH:49]=4)=[CH:47][CH:46]=[CH:45][CH:44]=5)=[O:40])=[C:23]([O:22][CH3:21])[CH:28]=3)[C:10]=12
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참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 22347095N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamideHCID 223473583-iodo-1-(3-morpholinopropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

생성물 1

HCID 22347025N2-{4-[4-amino-1-(3-morpholinopropyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide수율 56.2%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매
HCID 962Water용매
HCID 80711,2-Dimethoxyethane용매

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온도
80 °C

실험 절차

A solution of 3-iodo-1-(3-morpholinopropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.244 g, 0.629 mmol) in ethylene glycol dimethyl ether (16 mL) was treated with N2-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-methyl-1H-2-indolecarboxamide (0.281 g, 0.692 mmol), tetrakis(triphenylphosphine)palladium (0.044 g, 0.038 mmol), and a solution of sodium carbonate (0.160 g, 1.51 mmol) in water (8 mL). The reaction mixture was stirred for 4.5 h at 80° C. The organic solvent was removed under reduced pressure and ethyl acetate (200 mL) was added. The layers were partitioned and the aqueous layer was extracted with ethyl acetate (400 mL). The combined organic layers were dried over magnesium sulfate, filtered and evaporated under reduced pressure. The crude material was purified by flash chromatography on silica gel using a step-wise gradient of 10% methanol in dichloromethane to 50% methanol in dichloromethane as the eluent. The column afforded 0.191 g (56%) of pure N2-{4-[4-amino-1-(3-morpholinopropyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide. 1H NMR (DMSO-d6, 400 MHz) δ 9.440 (s, 1H), 8.260 (s, 1H), 8.1229-8.1026 (d, 1H, J=8.12 Hz), 7.7184-7.6986 (d, 1H, J=7.92 Hz), 7.5983-7.578 (d, 1H, J=8.08 Hz), 7.345-7.290 (m, 4H), 7.172-7.133 (m, 1H), 4.421-4386 (m, 2H), 4.04 (s, 3H), 3.958 (s, 3H), 3.521-3.500 (m, 4H), 2.349-2.314 (m, 6H), 2.035-2.001 (m, 2H); LCMS (Thermoquest AQA single-quad MS, Genesis C18 column, 3 μm particle size, 33×4.6 mm; 70% 50 mM ammonium acetate in water to 95% acetonitrile over 6 min, 0.8 to 0.5 mL/min) Rt 2.05 min (100%), MH+ 541.3.

후처리

  1. customThe organic solvent was removed under reduced pressure and ethyl acetate (200 mL)
  2. additionwas added
  3. customThe layers were partitioned
  4. extractionthe aqueous layer was extracted with ethyl acetate (400 mL)
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe crude material was purified by flash chromatography on silica gel using a step-wise gradient of 10% methanol in dichloromethane to 50% methanol in dichloromethane as the eluent

출처 및 근거

ORD 기록
ord-181fd01e01034fe0b8bac800f75b05eb
출처 데이터셋
uspto-grants-2008_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07332497B2

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