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N,N'-Dimethylethylenediamine → tert-butyl {4-[3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methyl-2-oxopyridin-1(2H)-yl]phenyl}carbamate

HRID 632848
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HRID 632848 반응식
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[C:13](=[O:19])[NH:14][CH:15]=[CH:16][C:17]=3[CH3:18])[CH2:9][CH2:8][C:6]=2[N:7]=1.[C:20]([O:24][C:25](=[O:34])[NH:26][C:27]1[CH:32]=[CH:31][C:30](I)=[CH:29][CH:28]=1)([CH3:23])([CH3:22])[CH3:21].CNCCNC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN1CCCC1=O.[Cu](I)I>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[C:13](=[O:19])[N:14]([C:30]4[CH:29]=[CH:28][C:27]([NH:26][C:25](=[O:34])[O:24][C:20]([CH3:22])([CH3:21])[CH3:23])=[CH:32][CH:31]=4)[CH:15]=[CH:16][C:17]=3[CH3:18])[CH2:9][CH2:8][C:6]=2[N:7]=1
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반응물 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 2773612tert-butyl N-(4-iodophenyl)carbamateHCID 1212495913-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpyridin-2(1H)-one

생성물 1

HCID 121261407tert-butyl {4-[3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methyl-2-oxopyridin-1(2H)-yl]phenyl}carbamate

시약·촉매·용매 2

HCID 83717Copper iodide촉매HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

A degassed solution of 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-4-methylpyridin-2(1H)-one (250 mg, 0.97 mmol), tert-butyl(4-iodophenyl)carbamate (200 mg, 0.97 mmol), N1,N2-dimethylethane-1,2-diamine (50 mg, 0.49 mmol), copper iodide (40 mg, 0.20 mmol), and potassium phosphate (410 mg, 1.94 mmol) in 2 mL of N-methylpyrrolidone was heated to 70° C. and stirred overnight (17 h). The reaction was complete and allowed to cool to room temperature. The reaction was extracted with EtOAc (3ט5 mL) and with NaHCO3 (2ט10 mL). The crude organic layers were combined, dried over anhydrous Na2SO4 (s), filtered and the concentrated in vacuo. The crude mixture was then purified using the ISCO flash chromatography system using an 0-100% EtOAc/100-0% Hexane gradient mixture. Following concentration of the appropriate fractions the desired product was collected as an off white solid (115 mg, 27%). 1H NMR (DMSO) δ: 9.52 (s, 1H), 7.92 (s, 1H), 7.45-7.52 (m, 2H), 7.41 (d, J=6.7 Hz, 1H), 7.24-7.31 (m, 2H), 6.28 (s, 2H), 6.17 (d, J=7.0 Hz, 1H), 3.96 (br. S, H), 3.29 (s, 2H), 2.66(t, j=5.3 Hz, 2H), 2.18 (s, 3H), 1.39 (s, 9H)

후처리

  1. extractionThe reaction was extracted with EtOAc (3ט5 mL) and with NaHCO3 (2ט10 mL)
  2. dry with materialdried over anhydrous Na2SO4 (s)
  3. filtrationfiltered
  4. concentrationthe concentrated in vacuo
  5. customThe crude mixture was then purified
  6. customwas collected as an off white solid (115 mg, 27%)

출처 및 근거

ORD 기록
ord-38a338a4704a49cc83c5bb3ddca243cd
출처 데이터셋
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09321766B1

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