Methanol → HCID 67305218, compound

HRID 1009112Notes

Reaction equation

HRID 1009112 reaction equation
[C:1](=O)([O-])[O-:2].[Cs+].[Cs+].C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C2C(=CC=CC=2)C=CC=1C(C)C)(C)(C)C.Cl[C:40]1[N:41]=[C:42]([CH2:70][C:71]([CH3:74])([CH3:73])[CH3:72])[CH:43]=[C:44]2[C@@H:49]([NH:50][CH2:51][C@@H:52]([OH:66])[C@@H:53]([NH:62][C:63](=[O:65])[CH3:64])[CH2:54][C:55]3[CH:60]=[CH:59][CH:58]=[C:57]([F:61])[CH:56]=3)[CH2:48][C:47]3([CH2:69][CH2:68][CH2:67]3)[O:46][C:45]=12.CO>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH3:72][C:71]([CH3:74])([CH3:73])[CH2:70][C:42]1[CH:43]=[C:44]2[C@@H:49]([NH:50][CH2:51][C@@H:52]([OH:66])[C@@H:53]([NH:62][C:63](=[O:65])[CH3:64])[CH2:54][C:55]3[CH:60]=[CH:59][CH:58]=[C:57]([F:61])[CH:56]=3)[CH2:48][C:47]3([CH2:69][CH2:68][CH2:67]3)[O:46][C:45]2=[C:40]([O:2][CH3:1])[N:41]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 10796Cesium carbonateHCID 86614120HCID 86614120, compoundHCID 86614121HCID 86614121, compound

Product 1

HCID 67305218HCID 67305218, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a 2 mL microwave vial is added cesium carbonate (283 mg, 869 μmol), di-tert-butyl(2-(2-isopropylnaphthalen-1-yl)-3,4,5,6-tetramethylphenyl)phosphine (71 mg, 159 μmol), palladium(II) acetate (33 mg, 145 μmol), and N-((1S,2R)-3-(((4′S)-8′-chloro-6′-(2,2-dimethylpropyl)-3′,4′-dihydrospiro[cyclobutane-1,2′-pyrano[2,3-c]pyridin]-4′-yl)amino)-1-((3-fluorophenyl)methyl)-2-hydroxypropyl)acetamide (75 mg, 145 μmol) were added and the vial was flushed with N2 5×, then methanol (160 μl, 3619 μmol) and toluene (1 mL) were added simultaneously. The reaction was heated in the microwave at 110° C. for 30 min. LCMS shows 100% conversion. The reaction mixture was filtered through a small plug of silica gel, and the residue purified by reverse phase HPLC on a Phenomenex Synergi column (5 micron, MAX-RP, 80 Å, 150×30 mm) eluting at 45 ml/min with an linear gradient of 10% (v/v) to 100% MeCN (0.1% v/v TFA) in water (0.1% TFA) over 30 minutes to give the title compound as a tan amorphous solid. MS m/z: 514.2 (M+1).

Workup

  1. additionwere added
  2. customthe vial was flushed with N2 5×
  3. filtrationThe reaction mixture was filtered through a small plug of silica gel
  4. customthe residue purified by reverse phase HPLC on a Phenomenex Synergi column (5 micron, MAX-RP, 80 Å, 150×30 mm)
  5. washeluting at 45 ml/min with an linear gradient of 10% (v/v) to 100% MeCN (0.1% v/v TFA) in water (0.1% TFA) over 30 minutes

Sources & evidence

ORD record
ord-74d42c6dbd7248b2a8ebf21acebdf2fd
Source dataset
uspto-grants-2011_07
Patent number
US07973047B2

Reaction notes

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