Cesium carbonate → HCID 67286851, compound

HRID 1753859Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([S:8][CH2:9][CH3:10])[C:5]([C:11]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[O:12])=[C:4]([CH3:22])[CH:3]=1.[OH:23][CH:24]1[CH2:27][NH:26][CH2:25]1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.[Cl-].[Na+].O>[CH2:9]([S:8][C:6]1[C:5]([C:11]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[O:12])=[C:4]([CH3:22])[CH:3]=[C:2]([N:26]2[CH2:27][CH:24]([OH:23])[CH2:25]2)[N:7]=1)[CH3:10]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 439 mg (1.2 mmol) 6-chloro-2-ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4-methyl-pyridine-3-carboxylic acid amide (synthesis is described in section b) of example 2), 284 mg (2.6 mmol) 3-hydroxy-azetidine, 2.1 g (6.5 mmol) Cs2CO3 and 149 mg (0.13 mmol) Pd(PPh3)2 in 1,4-dioxane (4 ml) was heated at 110° C. for 16 h. Subsequently the RM was diluted with brine (30 ml) and extracted with EtOAc (3×40 ml). The combined organic layers were dried over MgSO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 1:1) and subsequent crystallization (hexane/EtOAc) provided 66 mg (0.18 mmol, 15%) 2-ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-6-(3-hydroxy-azetidin-1-yl)-4-methyl-pyridine-3-carboxylic acid amide (example 7). [M+H]+376.1.

Workup

extractionextracted with EtOAc (3×40 ml)
dry with materialThe combined organic layers were dried over MgSO4
concentrationconcentrated in vacuo
customPurification of the residue
customby CC (hexane/EtOAc 1:1) and subsequent crystallization (hexane/EtOAc)

Sources & evidence

ORD record: ord-7904463a0fff4cf182e20d7e93f45d84
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09168259B2

Reaction notes

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