2,6-Lutidine → 6-Arylpyrido[2,3-d]pyrimidine deriv. 74

HRID 3484

반응식

HRID 3484 반응식
[NH2:1][C:2]1[C:3]([C:21]2[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:22]=2[Cl:28])=[CH:4][C:5]2[CH:10]=[N:9][C:8]([NH:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:18][CH3:19])[CH2:16][CH3:17])=[N:7][C:6]=2[N:20]=1.[H-].[Na+].C(OC([N:38]([CH2:51][CH3:52])[C:39](=[N:43]C(OC(C)(C)C)=O)SCC)=O)(C)(C)C.CC(OC(=O)N)(C)C.N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.C(=O)(O)[O-].[Na+]>CN(C=O)C.ClCCl>[Cl:28][C:22]1[CH:23]=[CH:24][CH:25]=[C:26]([Cl:27])[C:21]=1[C:3]1[C:2]([NH:1][C:39]([NH2:43])=[N:38][CH2:51][CH3:52])=[N:20][C:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:18][CH3:19])[CH2:16][CH3:17])[N:9]=[CH:10][C:5]=2[CH:4]=1

참가 물질

10

반응물 7

HCID 79372,6-LutidineHCID 24758Sodium hydrideHCID 65367Trimethylsilyl triflateHCID 77922tert-Butyl carbamateHCID 516892Sodium BicarbonateHCID 53281146-(2,6-dichlorophenyl)-2-N-[3-(diethylamino)propyl]pyrido[2,3-d]pyrimidine-2,7-diamine2회HCID 86752345N,N'-Bis(tert-butoxycarbonyl)-N-(ethyl)-S-(ethyl)isothiourea

생성물 1

HCID 53281766-Arylpyrido[2,3-d]pyrimidine deriv. 74수율 14.3%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회

실험 절차

To a solution of 7-amino-6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidine (42 mg) from Example 20 in DMF (1 mL) was added 60% sodium hydride suspension (5 mg), and the mixture was stirred at room temperature for 0.5 hour. To the reaction mixture was added N,N'-Bis(tert-butoxycarbonyl)-N-(ethyl)-S-(ethyl)isothiourea (37 mg), and the mixture was stirred for 18 hours. The reaction mixture was diluted with dichloromethane (50 mL) and washed with water (2×15 mL). The organic layer was dried with sodium sulfate and concentrated. The resulting oil was purified on silica gel, eluting with methanol:ethyl acetate:triethylamine (8.5:1.5:0.3) to afford a mixture of 7-amino-6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidine (40 mg) and [[[6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidin-7-yl]imino[[1,1-dimethylethoxy) carbonyl]amino]methyl]ethylamino]carbamic acid-1,1-dimethylethyl ester. This mixture was dissolved in anhydrous dichloromethane (0.5 mL) containing 2.6-lutidine (8 mg). Trimethylsilyl trifluoromethanesulfonate (6 mg) was added, and the mixture was stirred at room temperature for 30 hours. The mixture was poured into saturated aqueous sodium bicarbonate, extracted with dichloromethane, dried over sodium sulfate, and concentrated. The resulting oil was chromatographed on silica gel, eluting with methanol:ethyl acetate: triethylamine (8.5:1.5:0.3) to afford the title compound (7 mg), ESMS (1/4 MeOH/CH3CN+0.1% AcOH): m/z (relative intensity) 490.5 (MH+, 100), 491.5 (MH+ +1, 27), 492.5 (MH+ +2, 64).

후처리

  1. stirringthe mixture was stirred for 18 hours
  2. washwashed with water (2×15 mL)
  3. dry with materialThe organic layer was dried with sodium sulfate
  4. concentrationconcentrated
  5. customThe resulting oil was purified on silica gel
  6. washeluting with methanol:ethyl acetate:triethylamine (8.5:1.5:0.3)
  7. customto afford
  8. stirringthe mixture was stirred at room temperature for 30 hours
  9. extractionextracted with dichloromethane
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated
  12. customThe resulting oil was chromatographed on silica gel
  13. washeluting with methanol:ethyl acetate: triethylamine (8.5:1.5:0.3)

출처 및 근거

ORD 기록
ord-3c27caf508a841fda99b0fa1d4d3b784
출처 데이터셋
uspto-grants-1998_03
특허 번호
US05733913

연결된 노트

불러오는 중…