Potassium Phosphate, Tribasic → (2S)-methyl 2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-(2'-methyl-[1,1'-biphenyl]-3-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate

HRID 472837Notes

Reaction equation

HRID 472837 reaction equation
C1(P(C2CCCCC2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]2C(OC)=CC=CC=2OC)CCCCC1.C1(C)C=CC=CC=1B(O)O.[C:40]([O:44][C@@H:45]([C:50]1[C:51]([CH3:78])=[N:52][C:53]2[N:54]([N:68]=[C:69]([C:71]3[CH:76]=[CH:75][CH:74]=[C:73](Cl)[CH:72]=3)[CH:70]=2)[C:55]=1[C:56]1[C:57]([CH3:67])=[C:58]2[C:63](=[C:64]([F:66])[CH:65]=1)[O:62][CH2:61][CH2:60][CH2:59]2)[C:46]([O:48][CH3:49])=[O:47])([CH3:43])([CH3:42])[CH3:41].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:40]([O:44][C@@H:45]([C:50]1[C:51]([CH3:78])=[N:52][C:53]2[N:54]([N:68]=[C:69]([C:71]3[CH:72]=[C:73]([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=4[CH3:14])[CH:74]=[CH:75][CH:76]=3)[CH:70]=2)[C:55]=1[C:56]1[C:57]([CH3:67])=[C:58]2[C:63](=[C:64]([F:66])[CH:65]=1)[O:62][CH2:61][CH2:60][CH2:59]2)[C:46]([O:48][CH3:49])=[O:47])([CH3:43])([CH3:42])[CH3:41]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27332672-Methylphenyl boronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 66693011HCID 66693011, compound

Product 1

HCID 66693089(2S)-methyl 2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-(2'-methyl-[1,1'-biphenyl]-3-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetateYield 51.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To a 2-5 ml microwave tube was added dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (595 mg, 1.449 mmol), PALLADIUM(II) ACETATE (163 mg, 0.725 mmol), o-tolylboronic acid (296 mg, 2.174 mmol) and (2S)-methyl 2-(tert-butoxy)-2-(2-(3-chlorophenyl)-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (400 mg, 0.725 mmol) in DMF (1.5 mL), followed by 2M K3PO4 solution (200 μl). The reaction mixture was heated in a microwave reactor at 130° C. for 30 min. The reaction mixture was filtered and the filtrate was purified by silica gel chromatography to afford (225.6 mg, 51.2%) of the title compound. 1H NMR (500 MHz, CHLOROFORM-d) δ 7.86-7.76 (m, 2H), 7.42 (t, J=7.8 Hz, 1H), 7.29-7.26 (m, 5H), 6.88-6.86 (m, 2H), 4.99 (s, 1H), 4.39-4.27 (m, 2H), 3.64 (s, 3H), 2.83-2.70 (m, 5H), 2.26 (s, 3H), 2.22-2.13 (m, 2H), 1.84 (s, 3H), 1.16 (s, 9H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. customthe filtrate was purified by silica gel chromatography

Sources & evidence

ORD record
ord-a64beb03db994349811b12e7a1772713
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

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