Diisopropylamine → 2-(3-Hydroxyphenyl)-9-(1H-indol-4-YL)-8-oxo-8,9-dihydro-7H-purine-6-carboxamide

HRID 391695Notes

Reaction equation

HRID 391695 reaction equation
[NH2:1][C:2]1[C:3]([C:28]([O:30]C)=O)=[N:4][C:5](Cl)=[N:6][C:7]=1[NH:8][C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[CH:12][N:13]2S(C1C=CC=CC=1)(=O)=O.CO[C:34]([C:36]1N=C(Cl)N=[C:38](Cl)[C:37]=1[N+]([O-])=O)=[O:35].C(N[CH:51]([CH3:53])C)(C)C.COC(C1C([N+]([O-])=O)=C(NC2C=CC=C3C=2C=CN3S(C2C=CC=CC=2)(=O)=O)N=C(Cl)[N:59]=1)=O.[O:87]1[CH2:91]CCC1>CCOC(C)=O.CC(O)=O.[Fe]>[OH:35][C:34]1[CH:36]=[C:37]([C:5]2[N:6]=[C:7]3[C:2]([NH:1][C:91](=[O:87])[N:8]3[C:9]3[CH:17]=[CH:16][CH:15]=[C:14]4[C:10]=3[CH:11]=[CH:12][NH:13]4)=[C:3]([C:28]([NH2:59])=[O:30])[N:4]=2)[CH:38]=[CH:51][CH:53]=1

Participants

9

Reactant 5

HCID 7912DiisopropylamineHCID 8028Tetrahydrofuran2×HCID 10586879Methyl 2,6-dichloro-5-nitropyrimidine-4-carboxylateHCID 574747906-(1-Benzenesulfonyl-1H-indol-4-ylamino)-2-chloro-5-nitro-pyrimidine-4-carboxylic acid methyl esterHCID 86627729Methyl 5-amino-2-chloro-6-(1-(phenylsulfonyl)-1H-indol-4-ylamino)pyrimidine-4-carboxylate

Product 1

HCID 574747952-(3-Hydroxyphenyl)-9-(1H-indol-4-YL)-8-oxo-8,9-dihydro-7H-purine-6-carboxamideYield 69%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl 5-amino-2-chloro-6-(1-(phenylsulfonyl)-1H-indol-4-ylamino)pyrimidine-4-carboxylate. To a solution of methyl-2,4-dichloro-5-nitro-pyrimidine-6-carboxylate (2.0 g, 7.9 mmol) in tetrahydrofuran (20 mL) and diisopropylamine (2.3 mL, 13.05 mmol) was added amine (1.42 g, 5.22 mmol) in TETRAHYDROFURAN (5 mL) at −78° C. After warming to rt, only desired adduct was seen (MS (ESI) m/z 487.9[M+1]+). The reaction was diluted with EtOAc (100 mL) and washed with 5% HCl (aq, 100 mL). The EtOAc layer was separated, dried (Na2SO4), filtered, and concentrated. The crude 6-(1-benzenesulfonyl-1H-indol-4-ylamino)-2-chloro-5-nitro-pyrimidine-4-carboxylic acid methyl ester was subjected to silica gel chromatography (9:1 Hex in EtOAc) to afford 1.32 g (2.71 mmol, 52%) after concentration of the desired fractions. 6-(1-Benzenesulfonyl-1H-indol-4-ylamino)-2-chloro-5-nitro-pyrimidine-4-carboxylic acid methyl ester (1.32 g, 2.71 mmol) was then dissolved in AcOH (15 mL). To this solution was added Fe (s, 1.4 g). The mixture was stirred at 60° C. for 1H, after which LCMS showed the desired reduced product (MS (ESI) m/z 458.1 [M+1]+). The reaction was filtered and then concentrated. The crude residue was subjected to silica gel chromatography (4:1 Hex in EtOAc). Concentration of the desired fractions afforded the title compound (0.85 g, 1.86 mmol, 69%).

Workup

  1. washwashed with 5% HCl (aq, 100 mL)
  2. customThe EtOAc layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford 1.32 g (2.71 mmol, 52%) after concentration of the desired fractions
  7. filtrationThe reaction was filtered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-6eee1bc311314b85b11417036867d973
Source dataset
uspto-grants-2013_02
Patent number
US08383634B2

Reaction notes

Loading…