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

HRID 617999

Reaction equation

HRID 617999 reaction equation
[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

Participants

10

Reactant 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×HCID 86752345N,N'-Bis(tert-butoxycarbonyl)-N-(ethyl)-S-(ethyl)isothiourea

Product 1

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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

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-butoxy-carbonyl)-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). Trimethyl-silyl 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).

Workup

  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)

Sources & evidence

ORD record
ord-5c45eefd253b480ebc088e2c82cbe450
Source dataset
uspto-grants-1999_09
Patent number
US05952342

Linked notes

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