Cesium carbonate → 2-(1-((5-(2-methyl-1H-benzo[d]imidazol-1-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-ol

HRID 1922982Notes

Reaction equation

HRID 1922982 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:37]=[C:38]([N:56]2[CH2:61][CH2:60][O:59][CH2:58][CH2:57]2)[C:39]2[N:44]=[C:43]([CH2:45][N:46]3[CH2:51][CH2:50][CH:49]([C:52]([OH:55])([CH3:54])[CH3:53])[CH2:48][CH2:47]3)[S:42][C:40]=2[N:41]=1.[CH3:62][C:63]1[NH:67][C:66]2[CH:68]=[CH:69][CH:70]=[CH:71][C:65]=2[N:64]=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].O1CCOCC1>[CH3:62][C:63]1[N:67]([C:36]2[N:37]=[C:38]([N:56]3[CH2:57][CH2:58][O:59][CH2:60][CH2:61]3)[C:39]3[N:44]=[C:43]([CH2:45][N:46]4[CH2:51][CH2:50][CH:49]([C:52]([OH:55])([CH3:54])[CH3:53])[CH2:48][CH2:47]4)[S:42][C:40]=3[N:41]=2)[C:66]2[CH:68]=[CH:69][CH:70]=[CH:71][C:65]=2[N:64]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 119842-MethylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596055142-(1-((5-Chloro-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-ol

Product 1

HCID 498326052-(1-((5-(2-methyl-1H-benzo[d]imidazol-1-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-olYield 47.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A 5-20 mL microwave vial equipped with a magnetic follower was charged with Pd2(dba)3 (28 mg, 0.03 mmol), Xphos (58 mg, 0.12 mmol), 2-[1-(5-chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl)piperidin-4-yl]propan-2-ol (500 mg, 1.21 mmol), 2-methyl-1H-benzoimidazole (176 mg, 1.33 mmol), cesium carbonate (593 mg, 1.82 mmol) and dioxane (5 mL). 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 (25 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, 0-10% (2M NH3 in MeOH) in EtOAc) to give 223 as a red oil (290 mg, 47%). LCMS: (Method G): RT 6.76 min; [M+H]+ 508.4. 1H NMR (400 MHz, CHCl3-d): δ 8.10-8.05 (m, 1 H); 7.73-7.69 (m, 1 H); 7.32-7.26 (m, 2 H); 4.42 (m 4 H); 3.88 (t, J=4.6 Hz, 7 H); 3.11 (d, J=10.7 Hz, 2 H); 2.95 (s, 3 H); 2.31-2.19 (m, 2 H); 1.79 (d, J=12.7 Hz, 2 H); 1.50 (m, 2 H); 1.34 (m, 1 H); 1.22 (s, 6 H)

Workup

  1. customA 5-20 mL microwave vial equipped with a magnetic follower
  2. customThe reaction mixture was degassed for 5 min
  3. customirradiated at 150° C. for 30 min
  4. additionThe reaction mixture was diluted with MeOH
  5. washThe cartridge was washed with MeOH
  6. washthe desired product was eluted with 2M NH3 in MeOH
  7. customThe solvents were removed

Sources & evidence

ORD record
ord-1d4205600f8647568508da8a8cb87411
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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