Cesium carbonate → HCID 46215101, compound

HRID 62508Notes

Reaction equation

HRID 62508 reaction equation
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][O:14][CH3:15])=[O:12])[C:5]([Cl:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[N:26]([CH:27]([CH3:29])[CH3:28])[N:25]=[C:24]([CH2:30][OH:31])[CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[Cl:20][C:5]1[C:6]([NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([NH:13][O:14][CH3:15])=[O:12])=[CH:7][C:2]([NH:21][C:22]2[N:26]([CH:27]([CH3:28])[CH3:29])[N:25]=[C:24]([CH2:30][OH:31])[CH:23]=2)=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamideHCID 57516902[5-Amino-1-(propan-2-yl)-1H-pyrazol-3-yl]methanol

Product 1

HCID 46215101HCID 46215101, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A microwave tube was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide (188 mg, 0.602 mmol), [5-amino-1-(1-methylethyl)-1H-pyrazol-3-yl]methanol (140 mg, 0.90 mmol), cesium carbonate (589 mg, 1.81 mmol) and DMF (5 ml). The reaction mixture was degassed under nitrogen for 10 min and palladium (II) acetate (6.8 mg, 0.03 mmol) and BINAP (37.5 mg, 0.06 mmol) were added. The reaction mixture was heated in an oil bath at 90° C. for 5 hrs and then in a microwave at 150° C. for 40 min. It was evaporated and the residue was dissolved in MeOH, filtered thru celite and thru an Acrodisc and purified further using preparative Agilent HPLC (5 to 95% water:acetonitrile with 0.1% formic acid). Fractions were combined and evaporated. EtOAc was added to the brown oil residue. Then the mixture was heated and hexane was added dropwise. A light yellow precipitate crashed out upon sonication. It was filtered off and dried under vacuum at 40° C. for 12 hrs. LC-MS [M+H]+=431.2. 1H NMR (400 MHz, DMSO-d6) ppm 11.93 (br. s., 1 H) 9.54 (br. s., 1 H) 8.54 (s, 1 H) 7.96-8.01 (m, 1 H) 7.52-7.62 (m, 3 H) 7.11-7.16 (m, 1 H) 6.70 (s, 1 H) 6.10 (s, 1 H) 4.95 (t, J=5.81 Hz, 1 H) 4.43 (dt, J=13.14, 6.57 Hz, 1 H) 4.33 (d, J=5.56 Hz, 2 H) 3.71 (s, 3 H) 1.29 (d, J=6.57 Hz, 6 H).

Workup

  1. customThe reaction mixture was degassed under nitrogen for 10 min
  2. customIt was evaporated
  3. dissolutionthe residue was dissolved in MeOH
  4. filtrationfiltered
  5. custompurified further
  6. customevaporated
  7. additionEtOAc was added to the brown oil residue
  8. temperatureThen the mixture was heated
  9. additionhexane was added dropwise
  10. customA light yellow precipitate crashed out upon sonication
  11. filtrationIt was filtered off
  12. customdried under vacuum at 40° C. for 12 hrs

Sources & evidence

ORD record
ord-f16b19b74291420a965034a3c3df8ecb
Source dataset
uspto-grants-2016_09
Patent number
US09446034B2

Reaction notes

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