1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Tert-butyl (6-(5-(3-fluoro-2-((1-(2-hydroxyethyl)-4-phenylpiperidin-4-yl)methylcarbamoyl)pyridin-4-ylthio)thiazol-2-ylamino)pyridin-3-yl)methyl(methyl)carbamate

HRID 1800834Notes

Reaction equation

HRID 1800834 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([NH:17][C:18]2[S:19][C:20]([S:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26]([C:30](O)=[O:31])[C:25]=3[F:33])=[CH:21][N:22]=2)=[N:15][CH:16]=1)[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[NH2:55][CH2:56][C:57]1([C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=2)[CH2:62][CH2:61][N:60]([CH2:63][CH2:64][OH:65])[CH2:59][CH2:58]1.C(N(C(C)C)CC)(C)C>CN1C(=O)CCC1.O>[F:33][C:25]1[C:26]([C:30](=[O:31])[NH:55][CH2:56][C:57]2([C:66]3[CH:67]=[CH:68][CH:69]=[CH:70][CH:71]=3)[CH2:58][CH2:59][N:60]([CH2:63][CH2:64][OH:65])[CH2:61][CH2:62]2)=[N:27][CH:28]=[CH:29][C:24]=1[S:23][C:20]1[S:19][C:18]([NH:17][C:14]2[N:15]=[CH:16][C:11]([CH2:10][N:8]([CH3:9])[C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:12][CH:13]=2)=[N:22][CH:21]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 592004604-(2-(5-((Tert-butoxycarbonyl(methyl)amino)methyl)pyridin-2-ylamino)thiazol-5-ylthio)-3-fluoropicolinic acidHCID 592645442-(4-(Aminomethyl)-4-phenylpiperidin-1-yl)ethanol

Product 1

HCID 59321438Tert-butyl (6-(5-(3-fluoro-2-((1-(2-hydroxyethyl)-4-phenylpiperidin-4-yl)methylcarbamoyl)pyridin-4-ylthio)thiazol-2-ylamino)pyridin-3-yl)methyl(methyl)carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-(2-(5-((Tert-butoxycarbonyl(methyl)amino)methyl)pyridin-2-ylamino)thiazol-5-ylthio)-3-fluoropicolinic acid (0.120 g, 0.244 mmol) was diluted in NMP (4 mL) and treated with HOBT (0.043 g, 0.317 mmol), EDAC (0.094 g, 0.488 mmol) and 2-(4-(aminomethyl)-4-phenylpiperidin-1-yl)ethanol (0.074 g, 0.317 mmol) and diisopropylethylamine (0.213 mL, 1.22 mmol) at 23° C. The reaction was stirred overnight then water was added and this was extracted with ethyl acetate/THF (3×). The organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated to give a residue which was purified on preparative HPLC (acetonitrile/water/TFA). The title material was obtained (0.140 g, ˜81%) as a solid which was used as such for the next step. LC/MS (M+H)+: 708. Ret. time: 1.612 min. (Condition F).

Workup

  1. extractionthis was extracted with ethyl acetate/THF (3×)
  2. dry with materialThe organic extracts were dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue which
  6. customwas purified on preparative HPLC (acetonitrile/water/TFA)

Sources & evidence

ORD record
ord-4ff98fca08324c79b9145ec1b1146515
Source dataset
uspto-grants-2013_01
Patent number
US08343999B2

Reaction notes

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