Cesium fluoride → {4-{2-[(3R)-1-Aza-bicyclo[2.2.2]oct-3-yloxy]-pyrimidin-5-yl}-2-nitro-phenyl}-carbamic Acid tert-butyl Ester

HRID 970017Notes

Reaction equation

HRID 970017 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([O:8][C@@H:9]2[CH:14]3[CH2:15][CH2:16][N:11]([CH2:12][CH2:13]3)[CH2:10]2)=[N:6][CH:7]=1.[C:17]([O:21][C:22](=[O:42])[NH:23][C:24]1[CH:29]=[CH:28][C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][C:25]=1[N+:39]([O-:41])=[O:40])([CH3:20])([CH3:19])[CH3:18].[F-].[Cs+]>O1CCOCC1.CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:17]([O:21][C:22](=[O:42])[NH:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[CH:3]=[N:4][C:5]([O:8][C@@H:9]3[CH:14]4[CH2:15][CH2:16][N:11]([CH2:12][CH2:13]4)[CH2:10]3)=[N:6][CH:7]=2)=[CH:26][C:25]=1[N+:39]([O-:41])=[O:40])([CH3:20])([CH3:18])[CH3:19]

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 59737239Tert-butyl 2-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamateHCID 67070179(3R)-3-[(5-bromopyrimidin-2-yl)oxy]quinuclidine

Product 1

HCID 69435520{4-{2-[(3R)-1-Aza-bicyclo[2.2.2]oct-3-yloxy]-pyrimidin-5-yl}-2-nitro-phenyl}-carbamic Acid tert-butyl Ester

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

The product of Example 19A (0.57 g, 2.0 mmol) was coupled with the product of Example 34B (1.50 g, 4 mmol) under the catalysis of Pd2(dba)3 (24 mg, 0.025 mmol) and (tBu3P)2Pd (26 mg, 0.05 mmol) with CsF (Strem Chemicals, 1.80 g, 12.0 mmol) in dioxane (20 mL) and DMF (Aldrich, 2 mL) at 80° C. under N2 for 16 hours according to the procedure of Example 34C. The title compound was purified by chromatography (SiO2, EtOAc: MeOH (v. 2% NH3.H2O), 50:50, Rf. 0.3) as oil (590 mg, 67%). 1H NMR (300 MHz, MeOH-D4) δ 1.38 (s, 9 H), 1.46-1.59 (m, 1 H), 1.61-1.73 (m, 1 H), 1.74-1.88 (m, 1 H), 1.95-2.10 (m, 1 H), 2.22-2.33 (m, 1 H), 3.38-3.48 (m, 1 H), 5.15-5.25 (m, 1 H), 7.58 (d, J=8.2 Hz, 1 H), 7.97 (dd, J=8.8, 2.1 Hz, 1 H), 8.56 (d, J=4.9 Hz, 1 H), 8.97 (s, 2 H) ppm. MS (DCl/NH3): 442 (M+H)+.

Workup

  1. customThe title compound was purified by chromatography (SiO2, EtOAc: MeOH (v. 2% NH3.H2O), 50:50, Rf. 0.3) as oil (590 mg, 67%)

Sources & evidence

ORD record
ord-e38159a729994ecfbb97de12d45fa7ba
Source dataset
uspto-grants-2007_12
Patent number
US07309699B2

Reaction notes

Loading…