Cesium carbonate → HCID 59606006, compound

HRID 1923245Notes

Reaction equation

HRID 1923245 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[C:5]2[N:10]=[C:9]([CH2:11][C:12]([N:14]3[CH2:19][CH2:18][CH:17]([C:20]([OH:23])([CH3:22])[CH3:21])[CH2:16][CH2:15]3)=[O:13])[S:8][C:6]=2[N:7]=1.[CH2:30]([C:32]1[NH:33][C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1)[CH3:31].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]>[CH2:30]([C:32]1[N:33]([C:2]2[N:3]=[C:4]([N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)[C:5]3[N:10]=[C:9]([CH2:11][C:12]([N:14]4[CH2:19][CH2:18][CH:17]([C:20]([OH:23])([CH3:21])[CH3:22])[CH2:16][CH2:15]4)=[O:13])[S:8][C:6]=3[N:7]=2)[C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1)[CH3:31]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59606032HCID 59606032, compound

Product 1

HCID 59606006HCID 59606006, compoundYield 38.4%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A mixture of 2-(5-chloro-7-morpholin-4-yl-thiazolo[5,4-d]pyrimidin-2-yl)-1-[4-(1-hydroxy-1-methylethyl)piperidin-1-yl]ethanone (40 mg, 0.09 mmol), 2-ethylbenzimidazole (15 mg, 0.10 mmol), Pd2(dba)3 (2.1 mg, 2.5 mol %), Xphos (4.3 mg, 10 mol %) and Cs2CO3 (44 mg, 0.14 mmol) in dioxane (1.5 mL) was purged with argon gas then heated at 120° C., for 20 h, in a sealed tube. The reaction mixture diluted with EtOAc, filtered through Celite® and evaporated. The resulting residue was purified by column chromatography (Si—PCC, 0-10% MeOH in EtOAc) to give 549 as a pale beige solid (19 mg, 38%). LCMS (Method I): RT=3.47 min, [M+H]+ 550.2. 1H NMR (400 MHz, CHCl3-d): δ 8.02-7.98 (m, 1 H), 7.81-7.76 (m, 1 H), 7.33-7.29 (m, 2 H), 4.81-4.75 (m, 1 H), 4.52-4.29 (m, 4 H), 4.19 (s, 2 H), 4.07 (m, 1 H), 3.89-3.84 (m, 4 H), 3.38 (q, J=7.5 Hz, 2 H), 3.15-3.06 (m, 1 H), 2.63-2.54 (m, 1 H), 1.90-1.92 (m, 2 H), 1.92-1.80 (m, 2 H), 1.61-1.50 (m, 1 H), 1.44 (t, J=7.5 Hz, 3 H), 1.36-1.23 (m, 1 H), 1.20 (d, J=11.0 Hz, 6 H)

Workup

  1. customwas purged with argon gas
  2. additionThe reaction mixture diluted with EtOAc
  3. filtrationfiltered through Celite®
  4. customevaporated
  5. customThe resulting residue was purified by column chromatography (Si—PCC, 0-10% MeOH in EtOAc)

Sources & evidence

ORD record
ord-896b2c5fdd284b7bb4f9f0ffff7bd2f6
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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