Sodium hydride → HCID 67261316, compound

HRID 410665Notes

Reaction equation

[H-].[Na+].[OH:3][C:4]1([C:12]2[S:13][C:14]([C:17]3[CH:18]=[C:19]([N:24]([C:32]4[N:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[CH:34][N:33]=4)[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH:20]=[C:21]([CH3:23])[CH:22]=3)=[CH:15][N:16]=2)[CH2:10][CH2:9][C:8](=[O:11])[NH:7][CH2:6][CH2:5]1.Br[CH2:43][CH2:44][O:45][Si](C(C)(C)C)(C)C>CN(C=O)C>[OH:45][CH2:44][CH2:43][O:3][C:4]1([C:12]2[S:13][C:14]([C:17]3[CH:18]=[C:19]([N:24]([C:32]4[N:37]=[C:36]([C:38]([F:40])([F:41])[F:39])[CH:35]=[CH:34][N:33]=4)[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH:20]=[C:21]([CH3:23])[CH:22]=3)=[CH:15][N:16]=2)[CH2:10][CH2:9][C:8](=[O:11])[NH:7][CH2:6][CH2:5]1

Participants

Conditions

Temperature: 125 °C

Procedure

A flame dried microwave vessel was charged with a solution of sodium hydride (4.26 mg, 0.106 mmol, 2.0 equiv) in anhydrous DMF (1 ml). tert-butyl {3-[2-(4-hydroxy-7-oxoazepan-4-yl)-1,3-thiazol-5-yl]-5-methylphenyl}[4-(trifluoromethyl)pyrimidin-2-yl]carbamate (30 mg, 0.05 mmol) and (2-bromoethoxy)-tert-butyldimethylsilane (19.1 mg, 0.08 mmol, 1.5 equiv) were added, causing an exotherm and color change from tan to dark orange. This mixture was heated at 125° C. for 30 min. The resulting mixture of products was purified via reverse-phase HPLC (acetonitrile/water gradient with 0.05% TFA present), to afford tert-butyl (3-{2-[4-(2-hydroxyethoxy)-7-oxoazepan-4-yl]-1,3-thiazol-5-yl}-5-methylphenyl)[4-(trifluoromethyl)pyrimidin-2-yl]carbamate (14 mg, 33%), as an orange oil. MS ESI: [M+H]+ m/z 722.2

Workup

customA flame dried microwave vessel
additionThe resulting mixture of products
customwas purified via reverse-phase HPLC (acetonitrile/water gradient with 0.05% TFA present)

Sources & evidence

ORD record: ord-c4d185057fa643258544873ff989a3ec
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759366B2

Reaction notes

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