Water → HCID 11719814, compound

HRID 2110733Notes

Reaction equation

HRID 2110733 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[O:20][C:21]([CH3:24])=[N:22][N:23]=3)=[CH:15][CH:14]=2)[CH:3]=1.[C:25]([C:28]([C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1)([CH3:30])[CH3:29])([OH:27])=[O:26].C([O-])([O-])=O.[Cs+].[Cs+].O>COCCOC.C(#N)C>[CH3:9][O:8][C:6]1[N:7]=[C:2]([C:33]2[CH:32]=[C:31]([C:28]([CH3:30])([CH3:29])[C:25]([OH:27])=[O:26])[CH:36]=[CH:35][CH:34]=2)[CH:3]=[C:4]([NH:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[O:20][C:21]([CH3:24])=[N:22][N:23]=3)=[CH:15][CH:14]=2)[N:5]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 442489972-(3-Boronophenyl)-2-methylpropanoic acidHCID 86615703HCID 86615703, compound

Product 1

HCID 11719814HCID 11719814, compoundYield 25.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of (6-chloro-2-methoxy-pyrimidin-4-yl)-{2-[4-(5-methyl-[1,3,4]oxadiazol-2-yl)-phenyl]-ethyl}-amine (0.16 g, 0.46 mmol), 3-(1-carboxy-1-methyl-ethyl)-phenyl boronic acid, [125 mg, 0.6 mmol, see Example 49(b), step 2], and Cs2CO3 (0.37 g, 1.15 mmol) in ethylene glycol dimethyl ether (8 mL), acetonitrile (10 mL), and water (2 mL) is degassed by bubbling with Argon gas for 5 minutes, and treated with 1,1′-bis(diphenylphosphino)ferrocene palladium(II) chloride (20 mg) at room temperature. After 3 h at 85° C., the mixture is diluted with water (15 mL), and extracted with EtOAc (2×15 mL). The extracts are dried (MgSO4), filtered, and concentrated. The residue is chromatographed on SiO2 eluting with 80% EtOAc in heptane to afford 2-[3-(2-methoxy-6-{2-[4-(5-methyl-[1,3,4]oxadiazol-2-yl)-phenyl]-ethylamino}-pyrimidin-4-yl)-phenyl]-2-methyl-propionic acid [55 mg, Example 68]. LCMS: RT=1.82 minutes; MS: 474 (M+H); 1H NMR (300 MHz, CDCl3) □ 7.98-7.81 (4H, m), 7.5-7.27 (4H, m), 6.33 (1H, s), 3.97 (3H, s), 3.72-3.6 (2H, m), 2.92 (2H, t, J=6.5 Hz), 2.6 (3H, s), 1.6 (6H, s).

Workup

  1. customis degassed
  2. customby bubbling with Argon gas for 5 minutes
  3. additiontreated with 1,1′-bis(diphenylphosphino)ferrocene palladium(II) chloride (20 mg) at room temperature
  4. additionthe mixture is diluted with water (15 mL)
  5. extractionextracted with EtOAc (2×15 mL)
  6. dry with materialThe extracts are dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue is chromatographed on SiO2 eluting with 80% EtOAc in heptane

Sources & evidence

ORD record
ord-a27d4eec9dec45d1a83c12580a1dadc6
Source dataset
uspto-grants-2009_04
Patent number
US07517889B2

Reaction notes

Loading…