Diisopropylethylamine → HCID 89907007, compound

HRID 525745Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:26])[C:5]1[CH:10]=[C:9]([C:11](=[O:24])[NH:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=2)[CH:8]=[N:7][C:6]=1Cl)[CH3:2].[NH:27]1[CH2:31][CH2:30][C@@H:29]([OH:32])[CH2:28]1.CCN(C(C)C)C(C)C>CC(O)C>[CH2:1]([O:3][C:4](=[O:26])[C:5]1[CH:10]=[C:9]([C:11](=[O:24])[NH:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=2)[CH:8]=[N:7][C:6]=1[N:27]1[CH2:31][CH2:30][C@@H:29]([OH:32])[CH2:28]1)[CH3:2]

Participants

Conditions

Temperature: 22 °C

Procedure

A mixture of 2-chloro-5-((4-(trifluoromethoxy)phenyl)carbamoyl)nicotinic acid ethyl ester (Stage 72.5, 3.00 g, 7.7 mmol), (R)-3-pyrrolidinol (0.807 g, 9.26 mmol) and DIPEA (2.19 g, 17.0 mmol) in iPrOH (50 mL) was stirred at 22° C. for 60 min. The solvent was evaporated off under reduced pressure and the residue was dissolved in EtOAc, washed with sat. aq. NaHCO3 and brine, dried over anhydrous Na2SO4 and the solvent was evaporated off under reduced pressure to give the title compound as a foam. HPLC (Condition 4) tR=5.63 min, UPLC-MS (Condition 8) tR=1.06 min, m/z=440.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.32 (t, J=7.04 Hz, 3H), 1.79-2.01 (m, 2H), 3.09 (d, J=11.73 Hz, 1H), 3.41 (d, J=8.21 Hz, 1H), 3.54 (dd, J=11.73, 4.30 Hz, 1H), 3.65 (dd, J=10.17, 3.52 Hz, 1H), 4.25-4.39 (m, 3H), 4.96 (d, J=3.13 Hz, 1H), 7.34 (d, J=8.21 Hz, 2H), 7.78-7.90 (m, 2H), 8.36 (d, J=2.35 Hz, 1H), 8.81 (d, J=2.35 Hz, 1H), 10.28 (s, 1H).

Workup

customThe solvent was evaporated off under reduced pressure
dissolutionthe residue was dissolved in EtOAc
washwashed with sat. aq. NaHCO3 and brine
dry with materialdried over anhydrous Na2SO4
customthe solvent was evaporated off under reduced pressure

Sources & evidence

ORD record: ord-cbfe84d6d9a444208444158ba22922c5
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340537B2

Reaction notes

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