Dimethylformamide → HCID 59411413, compound

HRID 2068424Notes

Reaction equation

HRID 2068424 reaction equation
COC1N=C(C)C=CC=1C([O-])=O.CN(C=O)C.[C:18]([O:22][C:23]([N:25]([CH3:48])[C:26]([C:28]1[C:29]([C:41]2[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=2)=[N:30][N:31]2[CH:36]=[CH:35][C:34](B(O)O)=[C:33]([F:40])[C:32]=12)=[O:27])=[O:24])([CH3:21])([CH3:20])[CH3:19].Br[C:50]1[C:51]([CH3:62])=[N:52][C:53]([O:60][CH3:61])=[C:54]([CH:59]=1)[C:55]([O:57][CH3:58])=[O:56]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(N(CC)CC)C>[C:18]([O:22][C:23]([N:25]([CH3:48])[C:26]([C:28]1[C:29]([C:41]2[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=2)=[N:30][N:31]2[CH:36]=[CH:35][C:34]([C:50]3[C:51]([CH3:62])=[N:52][C:53]([O:60][CH3:61])=[C:54]([CH:59]=3)[C:55]([O:57][CH3:58])=[O:56])=[C:33]([F:40])[C:32]=12)=[O:27])=[O:24])([CH3:21])([CH3:20])[CH3:19]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 22678719HCID 22678719, compoundHCID 59411417HCID 59411417, compoundHCID 59411423HCID 59411423, compound

Product 1

HCID 59411413HCID 59411413, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

Methyl 5-(3-(tert-butoxycarbonyl)methyl)carbamoyl)-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-2-methoxy-6-methylnicotinate. To a degassed solution containing palladium (II) acetate (0.014 g, 0.063 mmol) and DMF (0.70 mL) was added 1,1′-Bis(diphenylphosphino)ferrocene. The solution was heated to 50° C. and maintained for 15 minutes. The solution was cooled to room temperature and 3-(tert-butoxycarbonyl(methyl)carbamoyl)-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-ylboronic acid (0.10 g, 0.21 mmol) and methyl 5-bromo-2-methoxy-6-methylnicotinate (0.054 g, 0.21 mmol) were added. Triethylamine was then added and the solution was heated at 90° C. for 3 h. The mixture was cooled to room temperature, filtered to remove solids and concentrated. Purification on silica gel (0-75% ethyl acetate/hexanes, 60 min gradient, 25 g column) afforded methyl 5-(3-(tert-butoxycarbonyl(methyl)carbamoyl)-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-2-methoxy-6-methylnicotinate as a white residue. 1H NMR (400 MHz, MeOD) δ ppm 8.60 (1H, d, J=7.03 Hz), 8.13 (1H, s), 7.77 (2H, d, J=3.26 Hz), 7.75 (1H, s), 7.24 (2H, s), 6.99 (1H, s), 4.07 (3H, s), 3.89 (3H, s), 3.29 (3H, s), 2.45 (3H, s), 1.01-1.13 (9H, m). LCMS retention time: 3.803 mM. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 3 micron, C18, 2.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 0.8 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where solvent A was 10% CH3CN/90% H2O/10 mM TFA and solvent B was 10% H2O/90% CH3CN/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 567 (MH+).

Workup

  1. temperaturemaintained for 15 minutes
  2. temperatureThe solution was cooled to room temperature
  3. temperaturethe solution was heated at 90° C. for 3 h
  4. temperatureThe mixture was cooled to room temperature
  5. filtrationfiltered
  6. customto remove solids
  7. concentrationconcentrated
  8. customPurification on silica gel (0-75% ethyl acetate/hexanes, 60 min gradient, 25 g column)

Sources & evidence

ORD record
ord-bc77554c22054bc18ed9f5afc610fa00
Source dataset
uspto-grants-2012_10
Patent number
US08293909B2

Reaction notes

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