Diisopropylethylamine → Methyl 5-{N-[(6-amino-5-iodopyridin-3-yl)carbonyl]-S-methylsulfonimidoyl}pentanoate

HRID 1778136Notes

Reaction equation

HRID 1778136 reaction equation
[CH3:1][S:2]([CH2:5][CH2:6][CH2:7][CH2:8][C:9]([O:11][CH3:12])=[O:10])(=[NH:4])=[O:3].[I:13][C:14]1[C:15]([NH2:23])=[N:16][CH:17]=[C:18]([CH:22]=1)[C:19](O)=[O:20].C(N(C(C)C)CC)(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>[NH2:23][C:15]1[N:16]=[CH:17][C:18]([C:19]([N:4]=[S:2]([CH2:5][CH2:6][CH2:7][CH2:8][C:9]([O:11][CH3:12])=[O:10])([CH3:1])=[O:3])=[O:20])=[CH:22][C:14]=1[I:13]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 114255416-Amino-5-iodonicotinic acidHCID 118130072methyl 5-(S-methylsulfonimidoyl)pentanoate

Product 1

HCID 118130089Methyl 5-{N-[(6-amino-5-iodopyridin-3-yl)carbonyl]-S-methylsulfonimidoyl}pentanoateYield 50.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of methyl 5-(S-methylsulfonimidoyl)pentanoate (2.32 g) was dissolved in anhydrous DMF (30 mL) and to this solution was added 5-iodo-6-amino-nicotinic acid (3.17 g, ˜1 eq), diisopropylethylamine (4.2 mL, 2 eq), and BOP (5.85 g, 1.1 eq). The reaction mixture was heated at 70° C. for 1 hour and then partitioned between EtOAc and aq NH4Cl. The organic layer was separated, washed sequentially with aq NH4Cl (1×), saturated aq NaHCO3 (1×), brine (1×), and dried with anhydrous Na2SO4 overnight. The upper solution layer was decanted, concentrated, and the brown oily reside was subject to column chromatography (acetone-CHCl3 1:100 to MeOH-acetone-CHCl3 1:2:50). Concentration of the product eluting fractions provided the title compound as a slight yellow colored foam (2.65 g).

Workup

  1. custompartitioned between EtOAc and aq NH4Cl
  2. customThe organic layer was separated
  3. washwashed sequentially with aq NH4Cl (1×), saturated aq NaHCO3 (1×), brine (1×)
  4. dry with materialdried with anhydrous Na2SO4 overnight
  5. customThe upper solution layer was decanted
  6. concentrationconcentrated
  7. washConcentration of the product eluting fractions

Sources & evidence

ORD record
ord-c9ddc0f6e35c4569958303d59c7180f9
Source dataset
uspto-grants-2016_02
Patent number
US09266869B2

Reaction notes

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