Cesium carbonate → HCID 67130049, compound

HRID 1038843Notes

Reaction equation

HRID 1038843 reaction equation
CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.C([O-])([O-])=O.[Cs+].[Cs+].[NH2:40][C:41]1[CH:49]=[C:48]2[C:44]([C:45]([CH3:57])=[N:46][N:47]2[C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])=[CH:43][CH:42]=1.Cl[C:59]1[N:60]=[C:61]([NH:68][CH:69]2[CH2:71][CH2:70]2)[C:62]2[O:67][CH:66]=[CH:65][C:63]=2[N:64]=1>C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:69]1([NH:68][C:61]2[C:62]3[O:67][CH:66]=[CH:65][C:63]=3[N:64]=[C:59]([NH:40][C:41]3[CH:49]=[C:48]4[C:44]([C:45]([CH3:57])=[N:46][N:47]4[C:50]([O:52][C:53]([CH3:54])([CH3:56])[CH3:55])=[O:51])=[CH:43][CH:42]=3)[N:60]=2)[CH2:71][CH2:70]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 18373193HCID 18373193, compoundHCID 866650932-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine

Product 1

HCID 67130049HCID 67130049, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

In a flask, RuPhos (3.63 g, 7.79 mmol) and Pd2dba3 (3.56 g, 3.89 mmol) were combined in t-AmOH (100 mL). The mixture was degassed by bubbling N2 into the solution. The mixture was heated to about 60° C. for about 30 min. Then Cs2CO3 (38.3 g, 117 mmol), tert-butyl 6-amino-3-methyl-1H-indazole-1-carboxylate (16.0 g, 64.9 mmol), and 2-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine (13.6 g, 64.9 mmol) were added in one portion. To the mixture was added t-AmOH (200 mL) and the mixture was placed under vacuum, purged with N2, and then stiffed at about 75° C. for about 15 h. The mixture was filtered through a plug of Celite®. The filtrate was concentrated and redissolved in DCM (50 mL). The mixture was purified by column chromatography (0-2.5% MeOH in DCM over 30 min on 330 g silica gel) to give a solid. The solid was dissolved in DCM (20 mL) and after about 10 min at rt, a thick precipitate formed which was collected via filtration. The solid was washed with DCM (25 mL) and dried in a vacuum oven at about 70° C. for about 12 h to give tert-butyl 6-(4-(cyclopropylamino)furo[3,2-d]pyrimidin-2-ylamino)-3-methyl-1H-indazole-1-carboxylate (12.5 g, 46%); LC/MS (Table 2, Method c) Rt=2.29 min.; MS m/z: 421 (M+H)+, 1H NMR (400 MHz, CDCl3) δ 8.76 (s, 1H), 7.64 (d, J=2.1 Hz, 1H), 7.50 (d, J=8.6 Hz, 1H), 7.42 (dd, J=8.6, 1.8 Hz, 1H), 7.26 (s, 1H), 6.67 (d, J=2.1 Hz, 1H), 5.29 (s, 1H), 3.20-3.12 (m, 1H), 2.55 (s, 3H), 1.72 (s, 9H), 0.99-0.91 (m, 2H), 0.71-0.64 (m, 2H).

Workup

  1. customThe mixture was degassed
  2. customby bubbling N2 into the solution
  3. custompurged with N2
  4. filtrationThe mixture was filtered through a plug of Celite®
  5. concentrationThe filtrate was concentrated
  6. dissolutionredissolved in DCM (50 mL)
  7. customThe mixture was purified by column chromatography (0-2.5% MeOH in DCM over 30 min on 330 g silica gel)
  8. customto give a solid
  9. customa thick precipitate formed which
  10. filtrationwas collected via filtration
  11. washThe solid was washed with DCM (25 mL)
  12. customdried in a vacuum oven at about 70° C. for about 12 h

Sources & evidence

ORD record
ord-407caf71953b4308bc033326668f5c68
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

Loading…