Cesium carbonate → 2-(1-((2-(2-methyl-1H-benzo[d]imidazol-1-yl)-4-morpholinofuro[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol

HRID 1945817Notes

Reaction equation

HRID 1945817 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[CH2:17][CH2:16][CH:15]([C:18]([OH:21])([CH3:20])[CH3:19])[CH2:14][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[CH2:17][CH2:16][CH:15]([C:18]([OH:21])([CH3:20])[CH3:19])[CH2:14][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 596060512-[1-(2-Chloro-4-morpholin-4-ylfuro[3,2-d]pyrimidin-6-ylmethyl)piperidin-4-yl]propan-2-ol

Product 1

HCID 596060932-(1-((2-(2-methyl-1H-benzo[d]imidazol-1-yl)-4-morpholinofuro[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-olYield 40%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-[1-(2-chloro-4-morpholin-4-ylfuro[3,2-d]pyrimidin-6-ylmethyl)piperidin-4-yl]propan-2-ol (110 mg, 0.28 mmol), 2-methyl-1H-benzoimidazole (42 mg, 0.32 mmol), Pd2dba3 (14 mg, 0.015 mmol), Xphos (15 mg, 0.031 mmol) and cesium carbonate (203 mg, 0.62 mmol) in DMF (2.5 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, 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 241 as a tan solid (55 mg, 40%). LCMS (Method G): RT=5.19 min, M+H+=491. 1H NMR (CDCl3, 400 MHz) δ 7.99 (m, 1 H); 7.71 (m, 1 H); 7.25 (m, 2 H); 6.77 (s, 1 H); 4.09 (t, J=4.7 Hz, 4 H); 3.89 (t, J=4.7 Hz, 4 H); 3.77 (s, 2 H); 3.11 (m, 2 H); 2.90 (s, 3 H); 2.16 (m, 2 H); 1.80 (m, 2 H); 1.49 (m, 2 H); 1.33-1.22 (m, 2 H) and 1.20 (s, 6 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-e25505bbe12e48cfb13373f7b967a7e4
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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