Cesium carbonate → 4-(5-(2-methyl-1H-benzo[d]imidazol-1-yl)-2-((3-(tetrahydro-2H-pyran-4-yl)azetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine

HRID 1945997Notes

Reaction equation

HRID 1945997 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[N:10]=[C:9]([CH2:11][N:12]3[CH2:15][CH:14](N4CCOCC4)[CH2:13]3)[S:8][C:6]=2[N:7]=1.[CH3:28][C:29]1[NH:30][C:31]2[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=2[N:33]=1.[CH3:38][CH:39]([C:41]1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=[C:43](C(C)C)[CH:42]=1)C.C([O-])([O-])=[O:73].[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[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)[C:5]3[N:10]=[C:9]([CH2:11][N:12]4[CH2:13][CH:14]([CH:41]5[CH2:42][CH2:43][O:73][CH2:38][CH2:39]5)[CH2:15]4)[S: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 596034604-(5-Chloro-2-((3-morpholinoazetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine

Product 1

HCID 596061024-(5-(2-methyl-1H-benzo[d]imidazol-1-yl)-2-((3-(tetrahydro-2H-pyran-4-yl)azetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholineYield 464.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
145 °C

Procedure

A mixture of 5-chloro-7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)-thiazolo[5,4-d]pyrimidine (100 mg, 0.24 mmol), 2-methylbenzimidazole (32 mg, 0.24 mmol), tris(dibenzylideneacetone)dipalladium (11 mg, 0.01 mmol), Xphos (12 mg, 0.02 mmol) and Cs2CO3 (159 mg, 0.48 mmol) in DMF (2 mL) was purged with argon then heated at 145° C. for 30 min in a microwave reactor. The reaction mixture was dissolved in EtOAc and washed with H2O (×6), then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-5%) to afford 482 as an orange solid (47 mg, 39%). LCMS (Method I): RT 2.59 min, [M+H]+ 507.2. 1H NMR (CDCl3, 400 MHz): δ 8.09-8.04 (m, 1 H); 7.73-7.68 (m, 1 H); 7.29-7.24 (m, 2 H); 4.41 (m, 4 H); 4.02 (s, 2 H); 3.88 (t, J=4.7 Hz, 4 H); 3.71 (m, 6 H); 3.17 (m, 3 H); 2.92 (s, 3 H) and 2.37 (m, 4 H)

Workup

  1. customwas purged with argon
  2. dissolutionThe reaction mixture was dissolved in EtOAc
  3. washwashed with H2O (×6)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-5%)

Sources & evidence

ORD record
ord-8f09ba476c164529a9b7e0507464131b
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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