Cesium carbonate → HCID 59548547, compound

HRID 1879684Notes

Reaction equation

HRID 1879684 reaction equation
C[N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[O:25])=[CH:20][N:19]=2)[C:3]1=O.Br[C:34]1[CH:41]=[CH:40][CH:39]=[C:38]([N:42]2[C:48](=[O:49])[C:47]3[CH:50]=[CH:51][C:52]([CH:54]4[CH2:56][CH2:55]4)=[CH:53][C:46]=3[NH:45][CH2:44][CH2:43]2)[C:35]=1[CH:36]=[O:37].[C:57](=[O:60])([O-])[O-].[Cs+].[Cs+].O1CCOCC1>CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.O>[CH:54]1([C:52]2[CH:51]=[CH:50][C:47]3[C:48](=[O:49])[N:42]([C:38]4[CH:39]=[CH:40][CH:41]=[C:34]([C:6]5[CH:5]=[C:4]([NH:17][C:18]6[CH:23]=[CH:22][C:21]([C:24]([N:26]7[CH2:27][CH2:28][O:29][CH2:30][CH2:31]7)=[O:25])=[CH:20][N:19]=6)[C:57](=[O:60])[N:2]([CH3:3])[CH:7]=5)[C:35]=4[CH:36]=[O:37])[CH2:43][CH2:44][NH:45][C:46]=3[CH:53]=2)[CH2:55][CH2:56]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 592164661-Methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-oneHCID 59548534HCID 59548534, compound

Product 1

HCID 59548547HCID 59548547, compoundYield 119%

Reagents, catalysts & solvents 2

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 962WaterSolvent

Procedure

A mixture of 1-Methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one (273 mg, 0.62 mmol, 1.2 eq), 2-Bromo-6-(8-cyclopropyl-5-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl)-benzaldehyde (200 mg, 0.52 mmol, 1 eq), X-Phos (6 mg, 0.012 mmol, 0.02 eq) Pd(dba)2 (11 mg, 0.019 mmol, 0.03 eq), Cesium carbonate (403 mg, 1.24 mmol, 2 eq) in 7 mL of a 6:1 mixture of dioxane:water was heated to 100 C for 14 hours under argon with stirring. The reaction was cooled, filtered through a sintered glass funnel, concentrated and directly loaded on a silica gel column, eluting with a gradient of 20 to 40% ethyl acetate in hexanes, followed by a gradient of 5 to 10% methanol in CH2Cl2 to give a solid, 383 mg of 2-(8-Cyclopropyl-5-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl)-6-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-benzaldehyde, 87%.

Workup

  1. temperatureThe reaction was cooled
  2. filtrationfiltered through a sintered glass funnel
  3. concentrationconcentrated
  4. washeluting with a gradient of 20 to 40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-ca2572cde63e462f92b7fbb306c7e01b
Source dataset
uspto-grants-2012_11
Patent number
US08318719B2

Reaction notes

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