Cesium carbonate → methyl 5-[(3-{[(1S)-1-(hydroxymethyl)propyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyrazine-2-carboxylate

HRID 1175922Notes

Reaction equation

HRID 1175922 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[OH:18][C:19]1[CH:20]=[C:21]([CH:31]=[C:32]([O:34][C@H:35]([CH2:38][OH:39])[CH2:36][CH3:37])[CH:33]=1)[C:22]([NH:24][C:25]1[CH:29]=[CH:28][N:27]([CH3:30])[N:26]=1)=[O:23]>C(#N)C>[OH:39][CH2:38][C@@H:35]([O:34][C:32]1[CH:33]=[C:19]([O:18][C:2]2[N:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:7]=2)[CH:20]=[C:21]([C:22]([NH:24][C:25]2[CH:29]=[CH:28][N:27]([CH3:30])[N:26]=2)=[O:23])[CH:31]=1)[CH2:36][CH3:37]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 406081Methyl 5-chloropyrazine-2-carboxylateHCID 591271493-hydroxy-5-{[(1S)-1-(hydroxymethyl)propyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Product 1

HCID 59127088methyl 5-[(3-{[(1S)-1-(hydroxymethyl)propyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyrazine-2-carboxylateYield 16.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
160 °C

Procedure

Methyl 5-chloropyrazine-2-carboxylate (104 mg, 0.60 mmol) and cesium carbonate (467 mg, 1.43 mmol) were added to a solution of 3-hydroxy-5-{[(1S)-1-(hydroxymethyl)propyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide (175 mg, 0.570 mmol), in acetonitrile (5 mL) and the mixture heated in a microwave reactor at 160° C. for 330 minutes. The acetonitrile was removed in vacuo and the residue dissolved in ethyl acetate (25 mL), washed with water (20 mL), brine (20 mL), dried (MgSO4) and evaporated to a residue which was chromatographed by preparative HPLC on C18 reversed phase, eluting with 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA), to give the required product (41 mg). 1H NMR δ (CDCl3): 0.97 (t, 3H), 1.78 (quin, 2H), 3.82 (s, 3H), 3.91 (s, 3H), 4.52 (m, 3H), 4.66 (quin, 1H), 6.59 (t, 1H), 6.89 (d, 1H), 7.05 (t, 1H), 7.15 (t, 1H), 8.19 (d, 1H), 8.79 (d, 1H), 9.86 (s, 1H); m/z 442 (M+H)+

Workup

  1. customThe acetonitrile was removed in vacuo
  2. dissolutionthe residue dissolved in ethyl acetate (25 mL)
  3. washwashed with water (20 mL), brine (20 mL)
  4. dry with materialdried (MgSO4)
  5. customevaporated to a residue which
  6. customwas chromatographed by preparative HPLC on C18 reversed phase
  7. washeluting with 5-95% acetonitrile (+0.2% TFA) in water (+0.2% TFA)

Sources & evidence

ORD record
ord-04e6fd4619174c02a4a6cc0182ab2dfe
Source dataset
uspto-grants-2010_11
Patent number
US07842694B2

Reaction notes

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