Cesium carbonate → 4-(1-((5-(2-ethyl-1H-benzo[d]imidazol-1-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)azetidin-3-yl)piperazin-2-one

HRID 1923358Notes

Reaction equation

HRID 1923358 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[C:5]2[N:10]=[C:9]([CH2:11][N:12]3[CH2:15][CH:14]([N:16]4[CH2:21][CH2:20][NH:19][C:18](=[O:22])[CH2:17]4)[CH2:13]3)[S:8][C:6]=2[N:7]=1.[CH2:29]([C:31]1[NH:32][C:33]2[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=2[N:35]=1)[CH3:30].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+]>O1CCOCC1.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]>[CH2:29]([C:31]1[N:32]([C:2]2[N:3]=[C:4]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[C:5]3[N:10]=[C:9]([CH2:11][N:12]4[CH2:13][CH:14]([N:16]5[CH2:21][CH2:20][NH:19][C:18](=[O:22])[CH2:17]5)[CH2:15]4)[S:8][C:6]=3[N:7]=2)[C:33]2[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=2[N:35]=1)[CH3:30]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596052704-[1-(5-Chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl)azetidin-3-yl]piperazin-2-one

Product 1

HCID 596054954-(1-((5-(2-ethyl-1H-benzo[d]imidazol-1-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)azetidin-3-yl)piperazin-2-oneYield 37%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
115 °C

Procedure

A mixture of 4-[1-(5-chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl)azetidin-3-yl]piperazin-2-one (315 mg, 0.74 mmol), 2-ethylbenzimidazole (120 mg, 0.82 mmol), tris(dibenzylideneacetone)dipalladium (17 mg, 0.02 mmol), XPhos (35 mg, 0.07 mmol) and Cs2CO3 (365 mg, 1.12 mmol) in dioxane (10 mL) was purged with argon then heated at 115° C. for 4 h then stirred at r.t. for 16 h. The reaction mixture was filtered through Celite®, washing with dioxane, and the filtrate concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, MeOH:DCM, 1-10%) affording 796 (146 mg, 37%). LCMS (method G): RT 4.90 min, [M+H]+ 534.3. 1H NMR (DMSO, 400 MHz): δ 7.99-7.99 (1 H, m), 7.75 (1 H, s), 7.64-7.63 (1 H, m), 7.26-7.25 (2 H, m), 4.32 (4 H, brd s), 4.04 (2 H, s), 3.79 (4 H, t, J=4.61 Hz), 3.57-3.52 (2 H, m), 3.31 (2 H, s), 3.25 (2 H, q, J=7.43 Hz), 3.18-3.14 (5 H, m), 2.87 (2 H, s), 1.32 (3 H, t, J=7.42 Hz)

Workup

  1. customwas purged with argon
  2. filtrationThe reaction mixture was filtered through Celite®
  3. washwashing with dioxane
  4. concentrationthe filtrate concentrated in vacuo
  5. customThe resulting residue was purified by column chromatography (Si-PCC, MeOH:DCM, 1-10%)

Sources & evidence

ORD record
ord-d6bc456917c1401ab2a523d934b21dfd
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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