Cesium carbonate → 2-(2-methyl-1H-benzo[d]imidazol-1-yl)-4-morpholino-6-((3-morpholinoazetidin-1-yl)methyl)furo[3,2-d]pyrimidine

HRID 1923001Notes

Reaction equation

HRID 1923001 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[O:10][C:9]([CH2:11][N:12]3[CH2:15][CH:14]([N:16]4[CH2:21][CH2:20][O:19][CH2:18][CH2:17]4)[CH2:13]3)=[CH:8][C:6]=2[N:7]=1.[CH3:28][C:29]1[NH:33][C:32]2[CH:34]=[CH:35][CH:36]=[CH:37][C:31]=2[N:30]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.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]>[CH3:28][C:29]1[N:33]([C:2]2[N:3]=[C:4]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[C:5]3[O:10][C:9]([CH2:11][N:12]4[CH2:15][CH:14]([N:16]5[CH2:21][CH2:20][O:19][CH2:18][CH2:17]5)[CH2:13]4)=[CH:8][C:6]=3[N:7]=2)[C:32]2[CH:34]=[CH:35][CH:36]=[CH:37][C:31]=2[N:30]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 119842-MethylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596052042-Chloro-4-morpholin-4-yl-6-(3-morpholin-4-ylazetidin-1-ylmethyl)furo[3,2-d]pyrimidine

Product 1

HCID 596058662-(2-methyl-1H-benzo[d]imidazol-1-yl)-4-morpholino-6-((3-morpholinoazetidin-1-yl)methyl)furo[3,2-d]pyrimidineYield 30.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-chloro-4-morpholin-4-yl-6-(3-morpholin-4-ylazetidin-1-ylmethyl)furo[3,2-d]pyrimidine (100 mg, 0.25 mmol), 2-methyl-1H-benzoimidazole (38 mg, 0.29 mmol), Pd2dba3 (12 mg, 0.013 mmol), Xphos (13 mg, 0.027 mmol) and cesium carbonate (184 mg, 0.56 mmol) in DMF (2.2 mL) was purged with argon gas then subjected to microwave irradiation at 145° C. for 30 min. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge (10 g), which was washed with MeOH/DCM before the desired product was eluted with 2 M NH3 in MeOH/DCM. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH 100:0 to 97:3 to 95:5 to 90:10) to afford 242 as a tan solid (37 mg, 30%). LCMS (Method G): RT=4.85 min, M+H+=490. 1H NMR (CDCl3, 400 MHz) δ 7.99 (m, 1H); 7.70 (m, 1 H); 7.26 (m, 2 H); 6.72 (s, 1 H); 4.07 (t, J=4.7 Hz, 4 H); 3.90-3.79 (m, 6H); 3.75 (m, 4 H); 3.64 (m, 2 H); 3.17 (m, 1 H); 3.11 (m, 1 H); 2.89 (s, 3 H) and 2.37 (m, 5 H)

Workup

  1. customwas purged with argon gas
  2. customirradiation at 145° C. for 30 min
  3. washwas washed with MeOH/DCM before the desired product
  4. washwas eluted with 2 M NH3 in MeOH/DCM
  5. customThe product was collected
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH 100:0 to 97:3 to 95:5 to 90:10)

Sources & evidence

ORD record
ord-c205f90c40e24a439d696905f8feadff
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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