1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-(2-hydroxy-2,2-diphenylethyl)-4-(2-(pyridine-2-ylamino)thiazol-5-ylthio)picolinamide

HRID 1685335Notes

Reaction equation

HRID 1685335 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[S:9][C:10]([S:13][C:14]2[CH:19]=[CH:18][N:17]=[C:16]([C:20]([OH:22])=O)[CH:15]=2)=[CH:11][N:12]=1.[NH2:23][CH2:24][C:25]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[OH:26].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN1C(=O)CCC1>[OH:26][C:25]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:24][NH:23][C:20](=[O:22])[C:16]1[CH:15]=[C:14]([S:13][C:10]2[S:9][C:8]([NH:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)=[N:12][CH:11]=2)[CH:19]=[CH:18][N:17]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2018282-Amino-1,1-diphenylethanolHCID 59200361HCID 59200361, compound

Product 1

HCID 24958489N-(2-hydroxy-2,2-diphenylethyl)-4-(2-(pyridine-2-ylamino)thiazol-5-ylthio)picolinamideYield 24%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of 4-(2-(pyridine-2-ylamino)thiazol-5-ylthio)picolinic acid (0.063 g, 0.19 mmol) and 2-amino-1,1-diphenylethanol (0.060 g, 0.28 mmol, 1.5 eq, described in Example D) in NMP (3 mL), was added EDAC (0.055 g, 0.28 mmol, 1.5 eq), HOBt (0.026 g, 0.19 mmol, 1 eq) and diisopropylethylamine (0.100 mL, 0.57 mmol, 3 eq). The resulting mixture was stirred at 23° C. for 3.5 h. The mixture was purified on preparative HPLC (ammonium acetate/water/acetonitrile) and freeze dried to give the title compound as a solid (0.024 mg, 24%). The product was converted to the HCl salt by dissolving it in ethyl acetate (2 mL) and tetrahydrofuran (2 mL) and treating the mixture with a solution of HCl (4.0 M in dioxane, 0.011 mL, 0.045 mmol, 1 eq). The mixture was concentrated, then diluted with water and lyophilized to give the HCl salt of the title material (0.029 g) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.10 (2H, d, J=5.56 Hz), 6.30 (1H, s), 7.01 (1H, dd, J=6.69 and 5.43 Hz), 7.11-7.20 (3H, m), 7.28 (4H, t, J=7.71 Hz), 7.37 (1H, dd, J=5.31, 2.02 Hz), 7.42-7.48 (4H, m), 7.66 (1H, d, J=1.52 Hz), 7.79 (1H, ddd, J=9.22, 6.32 and 1.89 Hz), 8.31 (1H, dd, J=5.43 and 1.39 Hz), 8.40 (1H, t, J=4.80 Hz), 8.41 (1H, d, J=4.8 Hz), 11.86 (1H, s). LC/MS (M+H)+: 526. Ret. time: 2.00 (Condition D). HRMS: calcd: 526.1371; found: 526.1387.

Workup

  1. customThe mixture was purified on preparative HPLC (ammonium acetate/water/acetonitrile)
  2. customfreeze dried

Sources & evidence

ORD record
ord-81098cd2a90540d6b01a229f070b7a8c
Source dataset
uspto-grants-2012_04
Patent number
US08148400B2

Reaction notes

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