Potassium Carbonate → HCID 46866598, compound

HRID 2069717Notes

Reaction equation

[CH3:1][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:32].[C:33]([C:37]1[CH:38]=[C:39]2[C:44](=[C:45]([F:47])[CH:46]=1)[C:43](=[O:48])[N:42]([C:49]1[CH:54]=[CH:53][CH:52]=[C:51](Cl)[C:50]=1[CH2:56][OH:57])[N:41]=[CH:40]2)([CH3:36])([CH3:35])[CH3:34].C(=O)([O-])[O-].[K+].[K+]>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].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[C:33]([C:37]1[CH:38]=[C:39]2[C:44](=[C:45]([F:47])[CH:46]=1)[C:43](=[O:48])[N:42]([C:49]1[CH:54]=[CH:53][CH:52]=[C:51]([C:6]3[CH:5]=[C:4]([NH:17][C:18]4[CH:23]=[CH:22][C:21]([C:24]([N:26]5[CH2:27][CH2:28][O:29][CH2:30][CH2:31]5)=[O:25])=[CH:20][N:19]=4)[C:3](=[O:32])[N:2]([CH3:1])[CH:7]=3)[C:50]=1[CH2:56][OH:57])[N:41]=[CH:40]2)([CH3:36])([CH3:34])[CH3:35]

Participants

Conditions

Temperature: 96 °C

Procedure

To a 2 mL vial were added 1-methyl-3-(5-(morpholine-4-carbonyl)pyridin-2-ylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one (171 mg, 0.39 mmol), 6-tert-Butyl-2-(3-chloro-2-hydroxymethyl-phenyl)-8-fluoro-2H-phthalazin-1-one (100 mg, 0.28 mmol), Potassium carbonate (76.6 mg, 0.55 mmol), tricyclohexylphosphine (4.7 mg, 16.6 μmol) and Pd(dba)2 (4.78 mg, 8.31 μmol). The vial was evacuated and backfilled with Nitrogen. This sequence was repeated three times. Then, 20% aqueous 1,4-dioxane, (1.5 ml) was added to the reaction mixture by syringe. The resulting mixture was heated to 96° C. for gentle reflux and stirred for 5 hr. After cooling down to room temperature, DCM (1 mL) and trithiocyanuric acid trisodium salt, 15% aqueous solution (1 ml) were added to the reaction mixture, then the resulting solution was stirred at 40° C. for 4 hr and additional for 4 hr after addition of 20 mg of activated carbon, then filtered through Celite pad and washed with DCM. DCM layer was collected by phase separation, and the aqueous layer was extracted with additional DCM. The combined organics were diluted with IPA, and DCM was distilled out completely. The desired product was crystallized out from IPA, collected by filtration and washed with IPA. The filter cake was dried under vacuum oven at 50° C. to afford 120 mg of the title compound (68% isolated yield) as a yellow solid. MS (ESI) 640 (M+H)+.

Workup

customThe vial was evacuated
additionThen, 20% aqueous 1,4-dioxane, (1.5 ml) was added to the reaction mixture by syringe
temperaturefor gentle reflux
temperatureAfter cooling down to room temperature
additionDCM (1 mL) and trithiocyanuric acid trisodium salt, 15% aqueous solution (1 ml) were added to the reaction mixture
stirringthe resulting solution was stirred at 40° C. for 4 hr and additional for 4 hr
additionafter addition of 20 mg of activated carbon
filtrationfiltered through Celite pad
washwashed with DCM
customDCM layer was collected by phase separation
extractionthe aqueous layer was extracted with additional DCM
additionThe combined organics were diluted with IPA, and DCM
distillationwas distilled out completely
customThe desired product was crystallized out from IPA
filtrationcollected by filtration
washwashed with IPA
customThe filter cake was dried under vacuum oven at 50° C.

Sources & evidence

ORD record: ord-7b2e280ebb8c4d7cb6e54abf2d2a7917
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08299077B2

Reaction notes

Loading…