Diisopropylethylamine → methyl 3-[N-({6-amino-5-[(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]amino}phenyl)ethynyl]pyridin-3-yl}carbonyl)-S-methylsulfonimidoyl]benzoate

HRID 607446Notes

Reaction equation

HRID 607446 reaction equation
[NH2:1][C:2]1[C:10]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([NH:19][C:20]([C:22]3[N:26]([CH3:27])[N:25]=[C:24]([CH3:28])[CH:23]=3)=[O:21])[CH:14]=2)=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][N:3]=1.[CH3:29][S:30]([C:33]1[CH:34]=[C:35]([CH:40]=[CH:41][CH:42]=1)[C:36]([O:38][CH3:39])=[O:37])(=[NH:32])=[O:31].C(N(CC)C(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>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:6]([N:32]=[S:30]([C:33]2[CH:34]=[C:35]([CH:40]=[CH:41][CH:42]=2)[C:36]([O:38][CH3:39])=[O:37])([CH3:29])=[O:31])=[O:7])=[CH:9][C:10]=1[C:11]#[C:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([NH:19][C:20]([C:22]2[N:26]([CH3:27])[N:25]=[C:24]([CH3:28])[CH:23]=2)=[O:21])[CH:14]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 576578676-Amino-5-{3-[(2,5-dimethyl-2H-pyrazole-3-carbonyl)-amino]-phenylethynyl}-nicotinic acidHCID 57657957Methyl 3-[imino(methyl)oxo-lambda6-sulfanyl]benzoate

Product 1

HCID 57657929methyl 3-[N-({6-amino-5-[(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]amino}phenyl)ethynyl]pyridin-3-yl}carbonyl)-S-methylsulfonimidoyl]benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 6-amino-5-[(3-{[(1,3-dimethyl-1H-pyrazol-5-yl)carbonyl]amino}phenyl)ethynyl]nicotinic acid (68 mg, 0.18 mmol), methyl 3-(S-methylsulfonimidoyl)benzoate (42 mg, 0.198 mmol), and N,N-diisopropylethylamine (0.063 ml, 0.36 mmol) in 1.5 ml DMF at room temperature was added benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphoniumhexafluorophosphate (88 mg, 0.198 mmol). The reaction was heated at 60° C. for 3.5 hours, then at 48° C. for 16.5 hours. The mixture was partitioned between EtOAc and dilute brine. The EtOAc layer was washed with NaHCO3 solution, dilute HCl, NaHCO3 solution, brine, dried with anhydrous Na2SO4 and rotary evaporated. The dark foam was chromatographed eluting with hexane/acetone yielding light pink solid (38 mg, 37%).

Workup

  1. customThe mixture was partitioned between EtOAc and dilute brine
  2. washThe EtOAc layer was washed with NaHCO3 solution, dilute HCl, NaHCO3 solution, brine
  3. dry with materialdried with anhydrous Na2SO4 and rotary evaporated
  4. customThe dark foam was chromatographed
  5. washeluting with hexane/acetone yielding light pink solid (38 mg, 37%)

Sources & evidence

ORD record
ord-47da800c9e604fdcb0b6e626e19b51d4
Source dataset
uspto-grants-2011_03
Patent number
US07915443B2

Reaction notes

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