Diisopropylethylamine → Methyl 3-{4-[N-({5-[(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]-amino}phenyl)ethynyl]pyridin-3-yl}carbonyl)-S-methylsulfonimidoyl]phenyl}-propanoate

HRID 391583Notes

Reaction equation

HRID 391583 reaction equation
[CH3:1][N:2]1[C:6]([C:7]([NH:9][C:10]2[CH:11]=[C:12]([C:16]#[C:17][C:18]3[CH:19]=[N:20][CH:21]=[C:22]([CH:26]=3)[C:23](O)=[O:24])[CH:13]=[CH:14][CH:15]=2)=[O:8])=[CH:5][C:4]([CH3:27])=[N:3]1.[CH3:28][S:29]([C:32]1[CH:37]=[CH:36][C:35]([CH2:38][CH2:39][C:40]([O:42][CH3:43])=[O:41])=[CH:34][CH:33]=1)(=[NH:31])=[O:30].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH3:1][N:2]1[C:6]([C:7]([NH:9][C:10]2[CH:11]=[C:12]([C:16]#[C:17][C:18]3[CH:26]=[C:22]([C:23]([N:31]=[S:29]([C:32]4[CH:33]=[CH:34][C:35]([CH2:38][CH2:39][C:40]([O:42][CH3:43])=[O:41])=[CH:36][CH:37]=4)([CH3:28])=[O:30])=[O:24])[CH:21]=[N:20][CH:19]=3)[CH:13]=[CH:14][CH:15]=2)=[O:8])=[CH:5][C:4]([CH3:27])=[N:3]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 57657822Methyl 3-[4-(S-methylsulfonimidoyl)phenyl]propanoateHCID 576579595-[(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]amino}phenyl)-ethynyl]nicotinic acid

Product 1

HCID 24955630Methyl 3-{4-[N-({5-[(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]-amino}phenyl)ethynyl]pyridin-3-yl}carbonyl)-S-methylsulfonimidoyl]phenyl}-propanoateYield 45%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 5-[(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]amino}phenyl)-ethynyl]nicotinic acid (0.149 g, 0.414 mmol) in DMF (4 mL) was treated with methyl 3-(4-(S-methylsulfonimidoyl)phenyl)propanoate (0.100 g, 0.414 mmol), followed by BOP (0.238 g, 0.539 mmol) and DIPEA (0.144 mL, 0.830 mmol). The reaction mixture was heated to 50° C. for 3 h. After allowing the reaction to cool to room temperature it was taken up in EtOAc (10 mL) and extracted with brine (3×10 mL). The EtOAc layer was then washed with saturated aqueous Na2CO3 (2×10 mL). The organic layer was dried over anhydrous Na2SO4(s), filtered and concentrated. The crude residue was purified via column chromatography (silica gel, gradient elution, EtOAc in Hexanes: 0% to 100% EtOAc) affording the title compound (0.108 g, 45%).

Workup

  1. customthe reaction
  2. temperatureto cool to room temperature it
  3. extractionextracted with brine (3×10 mL)
  4. washThe EtOAc layer was then washed with saturated aqueous Na2CO3 (2×10 mL)
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4(s)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified via column chromatography (silica gel, gradient elution, EtOAc in Hexanes: 0% to 100% EtOAc)

Sources & evidence

ORD record
ord-9c16cc16220142b3bc57ffac4bf34ae9
Source dataset
uspto-grants-2013_02
Patent number
US08383825B2

Reaction notes

Loading…