Cesium carbonate → HCID 59605259, compound

HRID 1923180Notes

Reaction equation

HRID 1923180 reaction equation
CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.Cl[C:36]1[N:44]=[C:43]2[C:39]([N:40]=[C:41]([CH2:46][N:47]3[CH2:52][CH2:51][CH:50]([C:53]([OH:56])([CH3:55])[CH3:54])[CH2:49][CH2:48]3)[N:42]2[CH3:45])=[C:38]([N:57]2[CH2:62][CH2:61][O:60][CH2:59][CH2:58]2)[N:37]=1.[F:63][C:64]1[C:65]([N+:71]([O-:73])=[O:72])=[C:66]([NH2:70])[CH:67]=[CH:68][CH:69]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].CN(C=O)C>[F:63][C:64]1[C:65]([N+:71]([O-:73])=[O:72])=[C:66]([NH:70][C:36]2[N:44]=[C:43]3[C:39]([N:40]=[C:41]([CH2:46][N:47]4[CH2:52][CH2:51][CH:50]([C:53]([OH:56])([CH3:54])[CH3:55])[CH2:49][CH2:48]4)[N:42]3[CH3:45])=[C:38]([N:57]3[CH2:58][CH2:59][O:60][CH2:61][CH2:62]3)[N:37]=2)[CH:67]=[CH:68][CH:69]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 27828343-Fluoro-2-nitroanilineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596034262-(1-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol

Product 1

HCID 59605259HCID 59605259, compoundYield 73.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

A microwave vial equipped with a magnetic follower was charged with Pd2(dba)3 (5.7 mg, 0.006 mmol), Xphos (11.9 mg, 0.025 mmol), 2-[1-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethyl)-piperidin-4-yl]-propan-2-ol (102 mg, 0.25 mmol), 3-fluoro-2-nitro-phenylamine (47 mg, 0.30 mmol), cesium carbonate (114 mg, 0.35 mmol) and DMF (1 mL). The vial was capped, the reaction mixture was degassed for 5 min and irradiated at 150° C. for 30 min. The reaction mixture was diluted with MeOH and loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was washed with MeOH and the desired product was eluted with 2M NH3 in MeOH. The solvents were removed and the residue was subjected to flash chromatography (Si—PCC, 0-5% MeOH in EtOAc) to give 2-{1-[2-(3-fluoro-2-nitrophenylamino)-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethyl]piperidin-4-yl}propan-2-ol as a red oil (97 mg, 73%). LCMS (Method H): RT 0.27 min and 3.18 min; [M+H]+ 529

Workup

  1. customA microwave vial equipped with a magnetic follower
  2. customThe vial was capped
  3. customthe reaction mixture was degassed for 5 min
  4. customirradiated at 150° C. for 30 min
  5. additionThe reaction mixture was diluted with MeOH
  6. washThe cartridge was washed with MeOH
  7. washthe desired product was eluted with 2M NH3 in MeOH
  8. customThe solvents were removed

Sources & evidence

ORD record
ord-6fd98a0dcad043758e71114e180440af
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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