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

HRID 3484

反応式

HRID 3484 の反応式
[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

参加物

10

反応物 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-diamine2 回HCID 86752345N,N'-Bis(tert-butoxycarbonyl)-N-(ethyl)-S-(ethyl)isothiourea

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-3c27caf508a841fda99b0fa1d4d3b784
出典データセット
uspto-grants-1998_03
特許番号
US05733913

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