Sulfamic Acid → HCID 21057869, compound

HRID 2216285Notes

Reaction equation

HRID 2216285 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])[C:5]([CH:14]=[O:15])=[CH:4][N:3]=1.S(=O)(=O)(O)N.Cl([O-])=O.[Na+].C(Cl)(=O)C(Cl)=O.[CH3:31][O:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37][NH2:38])=[CH:35][CH:34]=1>C1COCC1.O.C(Cl)Cl.CN(C=O)C>[CH3:31][O:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37][NH:38][C:14]([C:5]2[C:6]([NH:8][CH2:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[N:7][C:2]([Cl:1])=[N:3][CH:4]=2)=[O:15])=[CH:35][CH:34]=1

Participants

10

Reactant 5

HCID 5987Sulfamic AcidHCID 65578Oxalyl chlorideHCID 754524-MethoxybenzylamineHCID 21941886HCID 21941886, compoundHCID 23668197Sodium Chlorite

Product 1

HCID 21057869HCID 21057869, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-chloro-4-(2,2-dimethyl-propylamino)-pyrimidine-5-carbaldehyde (1.2 g, 5.27 mmol) in THF (20 ml) is added sulfamic acid (0.819 g, 8.4 mmol) at ambient temperature. To the mixture, sodium chlorite (1.43 g, 15.8 mmol) in water (10 ml) is added dropwise at 0° C. and the reaction mixture is allowed to warm to ambient temperature. After being stirred for 30 min. at ambient temperature, the reaction mixture is diluted with water and extracted with CH2Cl2. The combined extracts are washed with water, brine, dried over MgSO4 and concentrated under reduced pressure to afford crude acid (1.17 g). To a solution of the crude acid (0.5 g, 2.05 mmol) in CH2Cl2 (10 ml) are added oxalyl chloride (0.36 ml, 4.1 mmol) and catalytic amount of DMF successively at 0° C., and the mixture is allowed to warm to ambient temperature. After being stirred for 1 hour at ambient temperature, the mixture is transferred to a solution of p-methoxybenzylamine (2.25 g, 16.7 mmol) in THF (30 ml) at −10° C.–−20° C. and the reaction mixture is stirred for 1 hour. The reaction mixture is quenched with cold water and extracted with CH2Cl2. The combined extracts are washed with water, brine, dried over MgSO4 and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (eluent:n-hexane:AcOEt=2:1) give 2-chloro-4-(2,2-dimethyl-propylamino)-pyrimidine-5-carboxylic acid 4-methoxy-benzylamide. Rf=0.38 (n-hexane:AcOEt=2:1). 1H NMR (400 MHz, DMSO-d6) δ 1.01 (s, 9H), 3.35 (d, 2H), 3.81 (s, 3H), 4.52 (d, 2H), 6.23 (brs, 1H), 6.90 (d, 2H), 7.25 (d, 2H), 8.15 (s, 1H), 9.09 (brs, 1H).

Workup

  1. extractionextracted with CH2Cl2
  2. washThe combined extracts are washed with water, brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customto afford crude acid (1.17 g)
  6. temperatureto warm to ambient temperature
  7. stirringAfter being stirred for 1 hour at ambient temperature
  8. stirringthe reaction mixture is stirred for 1 hour
  9. customThe reaction mixture is quenched with cold water
  10. extractionextracted with CH2Cl2
  11. washThe combined extracts are washed with water, brine
  12. dry with materialdried over MgSO4
  13. concentrationconcentrated under reduced pressure
  14. customThe residue is purified by silica gel column chromatography (eluent:n-hexane:AcOEt=2:1)

Sources & evidence

ORD record
ord-9e4ca9333e6b4b1f8cba0a0d743d0e65
Source dataset
uspto-grants-2006_09
Patent number
US07112589B2

Reaction notes

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