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Sodium Carbonate Monohydrate → N1-[4-(4-amino-1 trityl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]-2-fluoro-4-trifluoromethylbenzamide

HRID 2056219
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HRID 2056219 반응식
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([C:12]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:3]=1.[CH3:31][O:32][C:33]1[CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=[CH:35][C:34]=1[NH:48][C:49](=[O:61])[C:50]1[CH:55]=[CH:54][C:53]([C:56]([F:59])([F:58])[F:57])=[CH:52][C:51]=1[F:60].O.C(=O)([O-])[O-].[Na+].[Na+]>O.COCCOC.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]([C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:3]=[C:2]([C:37]3[CH:36]=[CH:35][C:34]([NH:48][C:49](=[O:61])[C:50]4[CH:55]=[CH:54][C:53]([C:56]([F:58])([F:59])[F:57])=[CH:52][C:51]=4[F:60])=[C:33]([O:32][CH3:31])[CH:38]=3)[C:10]=12
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참가 물질

7

반응물 3

HCID 2735133Sodium Carbonate MonohydrateHCID 223468963-iodo-1-trityl-1H-pyrazolo[3,4-d]pyrimidin-4-amineHCID 22347319N1-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-fluoro-4-(trifluoromethyl)benzamide

생성물 1

HCID 22347211N1-[4-(4-amino-1 trityl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]-2-fluoro-4-trifluoromethylbenzamide수율 89.5%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

A mixture of 3-iodo-1-trityl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.10 g, 0.19 mmol), N1-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-fluoro-4-trifluoromethylbenzamide (0.13 g, 0.29 mmol), tetrakis(triphenylphosphine)palladium(0) (0.01 g, 0.01 mmol) and sodium carbonate monohydrate (0.06 mg, 0.48 mmol) in water (2 mL) and ethylene glycol dimethyl ether (4 mL) was heated at 85° C. overnight. The solvents were removed under reduced pressure. Water was added into the residue and the mixture was extracted with ethyl acetate three times. The combined organics were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and evaporated to yield a brown solid which was purified by flash column chromatography on silica using Isco system to provide N1-[4-(4-amino-1-trityl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]-2-fluoro-4-trifluoromethylbenzamide (0.12 g, 0.17 mmol) as a white solid: 1H NMR (DMSO-d6, 400 MHz) δ 9.89 (dd, 1H), 8.25(d, 1H), 8.28 (s, 1H), 8.00 (t, 1H), 7.94 (s, 1H), 7.88 (d, 1H), 7.73 (d, 1H), 7.24 (m, 15H), 3.90 (s, 3H); MS: MH+ 689.

후처리

  1. customThe solvents were removed under reduced pressure
  2. additionWater was added into the residue
  3. extractionthe mixture was extracted with ethyl acetate three times
  4. washThe combined organics were washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customto yield a brown solid which
  9. customwas purified by flash column chromatography on silica using Isco system

출처 및 근거

ORD 기록
ord-3cad9fd0b3b6421194839f1c0e28daac
출처 데이터셋
uspto-grants-2008_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07332497B2

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