N,N-Dimethylglycine → Methyl 4-({5-[(5-chloropyridin-2-yl)sulfanyl]-2-cyclopropyl-1,3-oxazol-4-yl}methoxy)benzoate

HRID 1519252Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([SH:8])=[N:6][CH:7]=1.CN(C)CC(O)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[C:25]1[O:29][C:28]([CH:30]2[CH2:32][CH2:31]2)=[N:27][C:26]=1[CH2:33][O:34][C:35]1[CH:44]=[CH:43][C:38]([C:39]([O:41][CH3:42])=[O:40])=[CH:37][CH:36]=1>[Cu]I.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8][C:25]2[O:29][C:28]([CH:30]3[CH2:32][CH2:31]3)=[N:27][C:26]=2[CH2:33][O:34][C:35]2[CH:44]=[CH:43][C:38]([C:39]([O:41][CH3:42])=[O:40])=[CH:37][CH:36]=2)=[N:6][CH:7]=1

Participants

Conditions

Temperature: 120 °C

Procedure

An oven-dried flask was charged with CuI (0.004 g, 0.02 mmol), 5-chloropyridine-2-thiol (0.015 g, 0.10 mmol), N,N-dimethylglycine (0.002 g, 0.02 mmol) and K3PO4 (0.048 g, 0.23 mmol), evacuated and backfilled with N2. Methyl 4-[(5-bromo-2-cyclopropyl-1,3-oxazol-4-yl)methoxy]benzoate (0.036 g, 0.10 mmol) and DMF (0.5 ml) was added under N2. The reaction mixture was heated at 120° C. overnight. The reaction was cooled to rt and filtered through a pad of silica gel eluting with EtOAc. The filtrate was concentrated and purified by reverse phase HPLC to give methyl 4-({5-[(5-chloropyridin-2-yl)sulfanyl]-2-cyclopropyl-1,3-oxazol-4-yl}methoxy)benzoate. 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J=2.5 Hz, 1H), 7.90 (d, J=8.7, 2H), 7.48 (dd, J=8.4, 2.5 Hz, 1H), 6.95 (d, 3=8.7 Hz, 2H), 6.87 (d, J=8.4 Hz, 1H), 5.05 (s, 2H), 3.88 (s, 3H), 2.12 (m, 1H), 1.10 (m, 4H); FIRMS exact mass calc for C20H17ClN2O4S [M+H]+: 417.0670; observed: 417.0671.

Workup

customevacuated
temperatureThe reaction was cooled to rt
filtrationfiltered through a pad of silica gel eluting with EtOAc
concentrationThe filtrate was concentrated
custompurified by reverse phase HPLC

Sources & evidence

ORD record: ord-2107f5f3fd1947a3bcbc9a154d141dc0
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073879B2

Reaction notes

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