1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-fluoro-N-(2-hydroxy-2-phenylpentyl)-4-(2-(pyridin-2-ylamino)thiazol-5-ylthio)picolinamide

HRID 1685338Notes

Reaction equation

[NH2:1][CH2:2][C:3]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([OH:7])[CH2:4][CH2:5][CH3:6].[F:14][C:15]1[C:16]([C:34](O)=[O:35])=[N:17][CH:18]=[CH:19][C:20]=1[S:21][C:22]1[S:26][C:25]([NH:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[N:24][CH:23]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN1C(=O)CCC1>[F:14][C:15]1[C:16]([C:34]([NH:1][CH2:2][C:3]([OH:7])([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:4][CH2:5][CH3:6])=[O:35])=[N:17][CH:18]=[CH:19][C:20]=1[S:21][C:22]1[S:26][C:25]([NH:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[N:24][CH:23]=1

Participants

Conditions

Temperature: 23 °C

Procedure

1-Amino-2-phenylpentan-2-ol (0.099 g, 0.45 mmol, 1.5 eq) was dissolved in NMP (3 mL) and to this solution was added 3-fluoro-4-(2-(pyridin-2-ylamino)thiazol-5-ylthio)picolinic acid (0.101 g, 0.30 mmol), EDAC (0.089 g, 0.45 mmol, 1.5 eq), HOBt (0.042 g, 0.30 mmol, 1 eq) and diisopropylethylamine (0.16 mL, 0903 mmol, 3 eq). The resulting mixture was stirred at 23° C. for 2 h. The mixture was then purified on preparative HPLC (ammonium acetate/water/acetonitrile) and freeze dried to give the title compound (0.0552 g, 36%). 1H NMR (400 MHz, DMSO-d6) δ ppm: 0.76 (3H, t, J=7.33 Hz), 0.84-0.96 (1H, m), 1.19-1.30 (1H, m), 1.68-1.79 (2H, m), 3.63 (2H, d, J=5.81 Hz), 5.29 (1H, s), 7.01 (1H, dd, J=6.82 and 5.56 Hz), 7.05 (1H, t, J=5.18 Hz), 7.12 (1H, d, J=8.34 Hz), 7.20 (1H, t, J=7.33 Hz), 7.31 (2H, t, J=7.71 Hz), 7.42-7.46 (2H, m), 7.78 (1H, td, J=7.77 and 1.89 Hz), 7.82 (1H, s), 8.22-8.26 (2H, m), 8.31 (1H, dd, J=5.05 and 1.01 Hz), 11.88 (1H, s). LC/MS (M+H)+: 510. HPLC ret. time (Condition J): 6.095 min. HRMS calcd: 510.1434; found: 510.1412.

Workup

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

Sources & evidence

ORD record: ord-35586f6e8aad49d49ecd0839ccee46af
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08148400B2

Reaction notes

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