Cesium carbonate → HCID 49818751, compound

HRID 1692877Notes

Reaction equation

HRID 1692877 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:13][N:14]3[CH2:19][CH2:18][CH:17]([N:20]4[CH2:24][CH2:23][CH2:22][C:21]4=[O:25])[CH2:16][CH2:15]3)[N:8]2[CH2:11][CH3:12])=[C:4]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[N:3]=1.[Si]([N:39]1[C:47]2[C:42](=[C:43](B(O)O)[C:44]([F:48])=[CH:45][CH:46]=2)[CH:41]=[CH:40]1)(C(C)(C)C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:11]([N:8]1[C:7]([CH2:13][N:14]2[CH2:19][CH2:18][CH:17]([N:20]3[CH2:24][CH2:23][CH2:22][C:21]3=[O:25])[CH2:16][CH2:15]2)=[N:6][C:5]2[C:9]1=[N:10][C:2]([N:39]1[C:47]3[C:42](=[CH:43][C:44]([F:48])=[CH:45][CH:46]=3)[CH:41]=[CH:40]1)=[N:3][C:4]=2[N:26]1[CH2:27][CH2:28][O:29][CH2:30][CH2:31]1)[CH3:12]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 57417002{1-[tert-Butyl(dimethyl)silyl]-5-fluoro-1H-indol-4-yl}boronic acidHCID 58439180HCID 58439180, compound

Product 1

HCID 49818751HCID 49818751, compoundYield 9.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
140 °C

Procedure

A mixture of 1-[1-(2-chloro-9-ethyl-6-morpholin-4-yl-9H-purin-8-ylmethyl)-piperidin-4-yl]-pyrrolidin-2-one (115 mg, 0.26 mmol), [1-(tert-butyldimethylsilanyl)-5-fluoro-1H-indol-4-yl]boronic acid (105 mg, 0.36 mmol), Pd(PPh3)4 (30 mg, 10 mol %) and cesium carbonate (167 mg, 0.51 mmol) in dioxane/water (5:2 mL) was purged with nitrogen gas then heated at 140° C., for 30 min, in a microwave reactor. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then eluted with 2 M NH3 in MeOH. The resulting residue was purified by column chromatography (Si-PPC, MeOH:DCM, gradient 0:100 to 07:93) to give 109 as a colourless oil (13 mg, 9%). LCMS (Method F) RT 8.15 min, [M+H]+ 547.3. 1H NMR (CDCl3, 400 MHz): δ 8.74 (dd, J=9.1, 4.8 Hz, 1H); 8.30 (d, J=3.6 Hz, 1H); 7.28-7.24 (m, 1H); 7.08-6.99 (m, 1H); 6.58 (d, J=3.6 Hz, 1H); 4.42-4.30 (m, 6H); 4.09-3.97 (m, 1H); 3.88 (t, J=4.75 Hz, 4H); 3.72 (s, 2H); 3.35 (t, J=7.0 Hz, 2H); 2.95 (d, J=11.3 Hz, 2H); 2.39 (t, J=8.1 Hz, 2H); 2.32-2.22 (m, 2H); 2.06-1.95 (m, 2H); 1.77-1.61 (m, 4H); 1.52 (t, J=7.15 Hz, 3H)

Workup

  1. customwas purged with nitrogen gas
  2. washwashed with MeOH
  3. washthen eluted with 2 M NH3 in MeOH
  4. customThe resulting residue was purified by column chromatography (Si-PPC, MeOH:DCM, gradient 0:100 to 07:93)

Sources & evidence

ORD record
ord-6a2cf1cd9b9545849d0796fa4c3b2731
Source dataset
uspto-grants-2012_04
Patent number
US08158625B2

Reaction notes

Loading…