Diisopropylamine → Ethyl {N-[(6-amino-5-iodopyridin-3-yl)carbonyl]-S-methylsulfonimidoyl}acetate

HRID 1778125Notes

Reaction equation

HRID 1778125 reaction equation
[CH2:1]([O:3][C:4](=[O:10])[CH2:5][S:6]([CH3:9])(=[NH:8])=[O:7])[CH3:2].[I:11][C:12]1[C:13]([NH2:21])=[N:14][CH:15]=[C:16]([CH:20]=1)[C:17](O)=[O:18].C(NC(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[NH2:21][C:13]1[N:14]=[CH:15][C:16]([C:17]([N:8]=[S:6]([CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:10])([CH3:9])=[O:7])=[O:18])=[CH:20][C:12]=1[I:11]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 114255416-Amino-5-iodonicotinic acidHCID 118152571Ethyl(S-methylsulfonimidoyl)acetate

Product 1

HCID 118152573Ethyl {N-[(6-amino-5-iodopyridin-3-yl)carbonyl]-S-methylsulfonimidoyl}acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of ethyl(S-methylsulfonimidoyl)acetate was dissolved in anhydrous DMF (1 mL) and treated with 5-iodo-6-amino-nicotinic acid (82 mg, 1.05 eq), diisopropylamine (0.1 mL, 2 eq), and BOP (149 mg, 1.1 eq) with stirring. The reaction mixture was heated to 70° C. for 6 hours and then partitioned between EtOAc and aq NH4Cl. The organic layer was separated, washed with saturated aq NaHCO3 (1×) and brine (1×), and dried over Na2SO4. The organic phase was filtered and concentrated. The residue as purified by gradient column chromatography (EtOAc-Hexane 1:9 to 2:3). Concentration of the product containing fractions provided the title compound as a brown oil (24 mg).

Workup

  1. custompartitioned between EtOAc and aq NH4Cl
  2. customThe organic layer was separated
  3. washwashed with saturated aq NaHCO3 (1×) and brine (1×)
  4. dry with materialdried over Na2SO4
  5. filtrationThe organic phase was filtered
  6. concentrationconcentrated
  7. customThe residue as purified by gradient column chromatography (EtOAc-Hexane 1:9 to 2:3)
  8. additionConcentration of the product containing fractions

Sources & evidence

ORD record
ord-e40b4a3e40d542059ab7252f610589dc
Source dataset
uspto-grants-2016_02
Patent number
US09266869B2

Reaction notes

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