Sodium Carbonate → tert-butyl-N-methyl-N-[1-oxo-1-[[5-pyrimidin-5-yl-6-[2-tri(propan-2-yl)silyl-ethynyl]pyridin-2-yl]amino]propan-2-yl]carbamate

HRID 535400Notes

Reaction equation

[C:1]([O:5][C:6](=[O:33])[N:7]([CH:9]([CH3:32])[C:10]([NH:12][C:13]1[CH:18]=[CH:17][C:16](Br)=[C:15]([C:20]#[C:21][Si:22]([CH:29]([CH3:31])[CH3:30])([CH:26]([CH3:28])[CH3:27])[CH:23]([CH3:25])[CH3:24])[N:14]=1)=[O:11])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[N:34]1[CH:39]=[C:38](B(O)O)[CH:37]=[N:36][CH:35]=1.C([O-])([O-])=O.[Na+].[Na+].O1CCOCC1>O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CO>[C:1]([O:5][C:6](=[O:33])[N:7]([CH3:8])[CH:9]([CH3:32])[C:10](=[O:11])[NH:12][C:13]1[CH:18]=[CH:17][C:16]([C:38]2[CH:39]=[N:34][CH:35]=[N:36][CH:37]=2)=[C:15]([C:20]#[C:21][Si:22]([CH:29]([CH3:31])[CH3:30])([CH:26]([CH3:28])[CH3:27])[CH:23]([CH3:25])[CH3:24])[N:14]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of tert-butyl-N-[1-[[5-bromo-6-[2-tri(propan-2-yl)silylethynyl]pyridin-2-yl]-amino]-1-oxopropan-2-yl]-N-methylcarbamate C1a (3.5 g, 6.5 mmol), pyrimidin-5-ylboronic acid (1.0 g, 7.8 mmol), Na2CO3 (1.4 g, 13.2 mmol), Dichlorobis(triphenylphosphine)palladium(II) (450 mg, 0.64 mmol), dioxane (20 ml), MeOH (5 ml) and water (3.5 ml) is stirred under argon atmosphere for 17 h at 80° C. The mixture is diluted with water and extracted with DCM. The combined organic layers are dried over MgSO4 and concentrated in vacuo. The product is purified by RP HPLC. Yield: 2.33 g (67%). HPLC-MS: M+H=538; tR=2.26 min (*Method—4).

Workup

extractionextracted with DCM
dry with materialThe combined organic layers are dried over MgSO4
concentrationconcentrated in vacuo
customThe product is purified by RP HPLC

Sources & evidence

ORD record: ord-4f63e138e343479a96c422c11a5bd43b
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08859541B2

Reaction notes

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