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

HRID 1177454Notes

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])=[C:22]([CH3:28])[CH:21]=1.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:22]1[CH:21]=[C:20]([C:17]2[S:16][C:14]3[C:13]([N:18]=2)=[CH:12][CH:11]=[C:10]([C:7]2([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH2:8][CH2:9]2)[N:15]=3)[CH:27]=[CH:26][C:23]=1[C:24]#[N:25]

Participants

Conditions

Temperature: 190 °C

Procedure

A mixture of 5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine (50.6 mg, 201 μmol), 4-bromo-2-methylbenzonitrile (47 mg, 241 μmol), PdCl2(AmPhos)2 (7.1 mg, 10 μmol), and cesium carbonate (196 mg, 602 μmol) in DMF (1.6 mL) was heated (microwave) under argon at 190° C. for 30 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 (10 mL), dried over sodium sulfate, filtered and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 10% EtOAc/hexanes) provided 2-methyl-4-(5-(1-phenyl-cyclopropyl)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 (10 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customChromatographic purification of the residue (silica gel, 10% EtOAc/hexanes)

Sources & evidence

ORD record: ord-37d4c4a1de564f708bf57382c0309ef2
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07842685B2

Reaction notes

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