1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Methyl 5-(N-{[6-amino-5-({3-[(2-fluoro-5-methylbenzoyl)amino]phenyl}ethynyl)pyridin-3-yl]carbonyl}-S-methylsulfonimidoyl)pentanoate

HRID 1778140Notes

Reaction equation

HRID 1778140 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]=[S:11]([CH2:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])([CH3:13])=[O:12])=[O:9])=[CH:4][C:3]=1[C:22]#[C:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([NH2:30])[CH:25]=1.[F:31][C:32]1[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][C:33]=1[C:34](O)=[O:35].CCN=C=NCCCN(C)C>ClC(Cl)C.CN(C1C=CN=CC=1)C>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]=[S:11]([CH2:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])([CH3:13])=[O:12])=[O:9])=[CH:4][C:3]=1[C:22]#[C:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([NH:30][C:34](=[O:35])[C:33]2[CH:37]=[C:38]([CH3:41])[CH:39]=[CH:40][C:32]=2[F:31])[CH:25]=1

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 2428292-Fluoro-5-methylbenzoic acidHCID 118130063Methyl 5-[N-({6-amino-5-[(3-aminophenyl)ethynyl]pyridin-3-yl}carbonyl)-S-methylsulfonimidoyl]pentanoate

Product 1

HCID 118130084Methyl 5-(N-{[6-amino-5-({3-[(2-fluoro-5-methylbenzoyl)amino]phenyl}ethynyl)pyridin-3-yl]carbonyl}-S-methylsulfonimidoyl)pentanoateYield 81.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 63651,1-DichloroethaneSolvent

Procedure

To the mixture of methyl 5-[N-({6-amino-5-[(3-aminophenyl)ethynyl]pyridin-3-yl}carbonyl)-S-methylsulfonimidoyl]pentanoate, (85.6 mg, 0.2 mmol, 1 eq) and 2-fluoro-5-methylbenzoic acid (32.7 mg, 1.05 eq) in dichloroethane (2 mL) at 60° C. was added catalytic amount of DMAP (5 mg, 0.2 eq) and EDCI (46.1 mg, 1.2 eq). The reaction was stirred at that temperature for 4 h and then cooled to room temperature. It was then partitioned between EtOAc and saturated aq NaHCO3. The organic layer was further washed with aq NH4Cl, brine and then dried with anhydrous sodium sulfate. The organic layer was decanted, concentrated, and the residue was subject to a gradient column chromatography (EtOAc-Hex 1:4 to neat EtOAc). The product containing fractions were concentrated to give the title compound as a white foam (92 mg).

Workup

  1. customIt was then partitioned between EtOAc and saturated aq NaHCO3
  2. washThe organic layer was further washed with aq NH4Cl, brine
  3. dry with materialdried with anhydrous sodium sulfate
  4. customThe organic layer was decanted
  5. concentrationconcentrated
  6. additionThe product containing fractions
  7. concentrationwere concentrated

Sources & evidence

ORD record
ord-2311142f81614eaca5013e483a228d8d
Source dataset
uspto-grants-2016_02
Patent number
US09266869B2

Reaction notes

Loading…