Cesium carbonate → (S)-tert-Butyl 2-(6-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrrolidine-1-carboxylate

HRID 1471117Notes

Reaction equation

[CH3:1][C:2]1([CH3:28])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:18]=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[C:14](B4OC(C)(C)C(C)(C)O4)[CH:15]=3)[CH:10]=2)[O:3]1.BrC1C=[C:32]2[N:38]=[C:37]([C@@H:39]3[CH2:43][CH2:42][CH2:41][N:40]3[C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[N:36]([CH2:51][O:52][CH2:53][CH2:54][Si:55]([CH3:58])([CH3:57])[CH3:56])[C:33]2=[N:34][CH:35]=1.N1(C([O-])=O)CC[CH2:61][CH2:60]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1COCC1.O>[CH3:1][C:2]1([CH3:28])[C:6]([CH3:7])([CH3:8])[O:5][B:4]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH:15]=[C:14]([C:13]2[CH:12]=[C:32]4[N:38]=[C:37]([C@@H:39]5[CH2:43][CH2:42][CH2:41][N:40]5[C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[N:36]([CH2:51][O:52][CH2:53][CH2:54][Si:55]([CH3:58])([CH3:57])[CH3:56])[C:33]4=[N:34][CH:35]=2)[CH:61]=[CH:60]3)[O:3]1

Participants

Conditions

Temperature: 120 °C

Procedure

In a microwave vial, 2,6-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalene (57 mg, 0.150 mmol), a mixture of (S)-tert-butyl 2-(6-bromo-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrrolidine-1-carboxylate and (S)-tert-butyl 2-(6-bromo-142-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)pyrrolidine-1-carboxylate (112 mg), cesium carbonate (147 mg, 0.450 mmol) and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (12.3 mg, 0.030 mmol) were dissolved into THF (3 mL) and water (0.3 mL). An additional 1.5 mL of THF was added and the reaction was sparged with bubbling nitrogen until ˜2 mL had evaporated away. To the clear solution was added palladium (II) acetate (3.37 mg, 0.015 mmol). The vial was flushed with nitrogen, sealed and then heated with microwave irradiation at 120° C. for 30 min. The reaction was diluted with EtOAc (˜3 mL) and washed with water (2 mL) and brine (2 mL). The reaction was dried (MgSO4), filtered and concentrated to a yellow oil which was purified by flash chromatography (12 g SiO2, 25-75% EtOAc/hexanes) to yield (2S,2′S)-tert-butyl 2,2′-(6,6′-(naphthalene-2,6-diyl)bis(3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-b]pyridine-6,2-diyl))dipyrrolidine-1-carboxylate (74 mg) as a clear colorless oil (mixture of SEM regioisomers) and (S)-tert-butyl 2-(6-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)-342-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrrolidine-1-carboxylate (32 mg) as a colorless oil (mixture of SEM regioisomers). Each was used without further purification.

Workup

customthe reaction was sparged with bubbling nitrogen until ˜2 mL
customhad evaporated away
customThe vial was flushed with nitrogen
customsealed
additionThe reaction was diluted with EtOAc (˜3 mL)
washwashed with water (2 mL) and brine (2 mL)
dry with materialThe reaction was dried (MgSO4)
filtrationfiltered
concentrationconcentrated to a yellow oil which
customwas purified by flash chromatography (12 g SiO2, 25-75% EtOAc/hexanes)
customto yield
customEach was used without further purification

Sources & evidence

ORD record: ord-396e57fdde99440bb06439d8fcb5f1f2
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09006455B2

Reaction notes

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