Cesium carbonate → 3-Methyl-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)benzonitrile

HRID 1177457Notes

Reaction equation

[C:1]1([C:7]2([C:10]3[N:15]=[C:14]4[S:16][CH:17]=[N:18][C:13]4=[CH:12][CH:11]=3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][C:21]=1[CH3:28].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH3:28][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][C:20]=1[C:17]1[S:16][C:14]2[C:13]([N:18]=1)=[CH:12][CH:11]=[C:10]([C:7]1([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:8][CH2:9]1)[N:15]=2)[C:24]#[N:25]

Participants

Conditions

Temperature: 190 °C

Procedure

A mixture of 5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine (48.3 mg, 191 μmol), 4-bromo-3-methylbenzonitrile (45.0 mg, 230 μmol), PdCl2(AmPhos)2 (6.78 mg, 9.57 μmol), and cesium carbonate (187 mg, 574 μmol) in DMF (1.6 mL) was heated (microwave) under argon at 190° C. for 40 min. The reaction mixture was then partitioned between EtOAc (40 mL) and water (15 mL). The organic layer was separated, washed with water and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-100% EtOAc/hexanes) furnished 3-methyl-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)benzonitrile as a light-yellow solid. MS (ESI) m/z: Calculated: 367.1; Observed: 368.1 (M++1).

Workup

customThe reaction mixture was then partitioned between EtOAc (40 mL) and water (15 mL)
customThe organic layer was separated
washwashed with water and brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customChromatographic purification of the residue (silica gel, 0-100% EtOAc/hexanes)

Sources & evidence

ORD record: ord-f186310df2a94c9bb646003c4693f727
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07842685B2

Reaction notes

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