Water → 6-(N-ethylmethylsulfonamido)-2-(4-fluorophenyl)-N-methyl-5-(3-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide

HRID 2068411Notes

Reaction equation

HRID 2068411 reaction equation
FC(F)(F)S(O[C:7]1[C:12]([N:13]([CH2:18][CH3:19])[S:14]([CH3:17])(=[O:16])=[O:15])=[CH:11][N:10]2[N:20]=[C:21]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[C:22]([C:23](=[O:26])[NH:24][CH3:25])=[C:9]2[CH:8]=1)(=O)=O.[N:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[C:42]1([NH:45][C:46](=[O:62])[C:47]2[CH:52]=[CH:51][CH:50]=[C:49](B3OC(C)(C)C(C)(C)O3)[CH:48]=2)[CH2:44][CH2:43]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1>[CH2:18]([N:13]([C:12]1[C:7]([C:51]2[CH:50]=[CH:49][CH:48]=[C:47]([C:46](=[O:62])[NH:45][C:42]3([C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][N:36]=4)[CH2:43][CH2:44]3)[CH:52]=2)=[CH:8][C:9]2[N:10]([N:20]=[C:21]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[C:22]=2[C:23]([NH:24][CH3:25])=[O:26])[CH:11]=1)[S:14]([CH3:17])(=[O:15])=[O:16])[CH3:19]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 67417766HCID 67417766, compoundHCID 86639963HCID 86639963, compound

Product 1

HCID 468425086-(N-ethylmethylsulfonamido)-2-(4-fluorophenyl)-N-methyl-5-(3-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

6-(N-ethylmethylsulfonamido)-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl trifluoromethanesulfonate (0.1 g, 0.17 mmol, 1 eq), N-(1-(pyridin-2-yl)cyclopropyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.0.65 g, 0.18 mmol, 1.1 eq), tetrakistriphenylphosphine palladium (0.0058 g, 0.0051 mmol, 0.03 eq) and cesium carbonate (0.165 g, 0.51 mmol, 3 eq) were dissolved in 1,4-dioxane (10 ml) and water (2 ml) and the reaction was heated at 90° C. for 14 hours. The solution was filtered through celiete. Water was added to the filtrate which was then extracted with ethyl acetate. The organic layer was concentrated and the residue obtained purified by Preparative HPLC. Yield: 22 mg (26%) 1HNMR (400 MHz, CD3OD): δ 1.05 (t, J=8 Hz, 3H), 1.65-1.66 (m, 2H), 1.78-1.82 (m, 2H), 2.89 (s, 3H), 3.20 (s, 3H), 3.62 (br s, 2H), 7.28-7.30 (t, J=7.76 Hz, 2H), 7.57 (br s, 1H), 7.67 (t, J=7.72 Hz, 1H), 7.75 (d, J=8.20 Hz, 1H), 7.86-7.88 (m, 3H), 7.96 (s, 1H), 8.02 (d, J=2.09 Hz, 1H), 8.18 (br, 1H), 8.23 (s, 1H), 8.55 (d, J=5.32 Hz, 1H), 8.98 (s, 1H). LCMS: (ES+) m/z=627.2 (M+H); Method: Column-Ascentis Express C18 (5×2.1 mm-2.7 μm); Mphase A: 2% MeCN-98% H2O-10 mM NH4COOH; Mphase B: 98% MeCN-2% H2O-10 mM NH4COOH; Flow: 1 mL/Min; RT min: 1.768;

Workup

  1. filtrationThe solution was filtered through celiete
  2. additionWater was added to the filtrate which
  3. extractionwas then extracted with ethyl acetate
  4. concentrationThe organic layer was concentrated
  5. customthe residue obtained
  6. custompurified by Preparative HPLC
  7. customRT min

Sources & evidence

ORD record
ord-89f3489c8e7e4763b39e09e3ea047873
Source dataset
uspto-grants-2012_10
Patent number
US08293909B2

Reaction notes

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