Cesium carbonate → HCID 59605654, compound

HRID 1923136Notes

Reaction equation

HRID 1923136 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][CH2:12][N:13]3[CH2:18][CH2:17][CH:16]([C:19]([OH:22])([CH3:21])[CH3:20])[CH2:15][CH2:14]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][CH2:12][N:13]4[CH2:18][CH2:17][CH:16]([C:19]([OH:22])([CH3:21])[CH3:20])[CH2:15][CH2:14]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 59605650HCID 59605650, compound

Product 1

HCID 59605654HCID 59605654, compoundYield 56%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A mixture of 2-{1-[2-(5-chloro-7-morpholin-4-yl-thiazolo[5,4-d]pyrimidin-2-yl)ethyl]-piperidin-4-yl}propan-2-ol (56 mg, 0.13 mmol), 2-ethylbenzimidazole (21 mg, 0.15 mmol), Pd2(dba)3 (3.0 mg, 2.5 mol %), Xphos (6.3 mg, 10 mol %) and Cs2CO3 (64 mg, 0.20 mmol) in dioxane (1.0 mL) was purged with argon gas then heated at 120° C., for 18 h, in a sealed tube. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then the desired product eluted with 2 M NH3 in MeOH. The resulting residue was purified by flash chromatography (Si—PCC, 0-10% MeOH in DCM) to give 433 (39 mg, 56%) as an orange solid. LCMS: (Method I): RT 2.71 min; [M+H]+ 536.4. 1H NMR (400 MHz, CHCl3-d): δ 8.01-7.97 (m, 1 H), 7.76-7.71 (m, 1 H), 7.29-7.24 (m, 2 H), 4.52-4.32 (m, 4H), 3.90-3.85 (m, 4 H), 3.34 (q, 7.5 Hz, 2 H), 3.35-3.23 (m, 2 H), 3.21-3.10 (m, 2 H), 2.87-2.83 (m, 2 H), 2.17-2.05 (m, 2 H), 1.86-1.75 (m, 2 H), 1.43 (t, J=7.5 Hz, 3 H), 1.38-1.23 (m, 3 H), 1.22 (s, 6 H)

Workup

  1. customwas purged with argon gas
  2. washwashed with MeOH
  3. washthe desired product eluted with 2 M NH3 in MeOH
  4. customThe resulting residue was purified by flash chromatography (Si—PCC, 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-d894066f7a744c35ae23e008a66886bc
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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