Sodium Carbonate → HCID 86580534, compound

HRID 523293Notes

Reaction equation

HRID 523293 reaction equation
Br[C:2]1[C:14]2[C:13]3[C:8](=[CH:9][C:10]([C:15]([OH:18])([CH3:17])[CH3:16])=[CH:11][CH:12]=3)[NH:7][C:6]=2[C:5]([C:19]([NH2:21])=[O:20])=[CH:4][C:3]=1[Cl:22].[F:23][C:24]1[CH:29]=[CH:28][C:27]([N:30]2[CH:35]=[CH:34][C:33](=[O:36])[N:32]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39](B4OC(C)(C)C(C)(C)O4)[C:38]=3[CH3:52])[C:31]2=[O:53])=[CH:26][CH:25]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.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>[Cl:22][C:3]1[CH:4]=[C:5]([C:19]([NH2:21])=[O:20])[C:6]2[NH:7][C:8]3[C:13]([C:14]=2[C:2]=1[C:39]1[CH:40]=[CH:41][CH:42]=[C:37]([N:32]2[C:33](=[O:36])[CH:34]=[CH:35][N:30]([C:27]4[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=4)[C:31]2=[O:53])[C:38]=1[CH3:52])=[CH:12][CH:11]=[C:10]([C:15]([OH:18])([CH3:17])[CH3:16])[CH:9]=3

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 1177612874-bromo-3-chloro-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide2×HCID 123876129HCID 123876129, compound2×

Product 1

HCID 86580534HCID 86580534, compoundYield 49%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-bromo-3-chloro-7-(2-hydroxypropan-2-yl)-9H -carbazole-1-carboxamide [Intermediate 3] (135 mg, 0.354 mmol), 1-(4-fluorophenyl)-3-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidine-2,4(1H,3H)-dione [Intermediate 44] (164 mg, 0.389 mmol), and tetrakis(triphenylphosphine)palladium (20 mg, 0.018 mmol) in toluene (5.3 mL) and ethanol (1.8 mL) was bubbled with argon for several min. The mixture was treated with 2 M aqueous Na2CO3 (354 μl, 0.707 mmol), bubbled again with argon, and heated at 90° C. for 16 h. The cooled mixture was partitioned between EtOAc and water. The organic phase was dried and concentrated. The residue was purified by column chromatography on silica gel (24 g), eluting with EtOAc-hexanes (gradient from 25-100%), to give 3-chloro-4-(3-(3-(4-fluorophenyl)-2,6-dioxo-2,3-dihydropyrimidin-1(6H)-yl)-2-methylphenyl)-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide (mixture of four atropisomers) as a white solid (103 mg, 49% yield). Mass spectrum m/z 579 (M+H—H2O)+. 1H NMR (500 MHz, DMSO-d6) δ 11.52 (d, J=4.5 Hz, 1H), 8.29 (br. s., 1H), 8.13 (d, J=2.5 Hz, 1H), 7.91 (dd, J=7.9, 6.4 Hz, 1H), 7.85-7.80 (m, 1H), 7.64-7.54 (m, 3H), 7.53-7.45 (m, 2H), 7.36 (dt, J=11.9, 8.7 Hz, 2H), 7.25 (ddd, J=7.3, 4.3, 1.2 Hz, 1H), 7.03-6.83 (m, 1H), 6.73-6.47 (m, 1H), 5.97 (dd, J=7.9, 3.5 Hz, 1H), 5.04-4.92 (m, 1H), 1.75 (d, J=1.5 Hz, 3H), 1.47-1.33 (m, 6H).

Workup

  1. customwas bubbled with argon for several min
  2. custombubbled again with argon
  3. customThe cooled mixture was partitioned between EtOAc and water
  4. customThe organic phase was dried
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel (24 g)
  7. washeluting with EtOAc-hexanes (gradient from 25-100%)

Sources & evidence

ORD record
ord-0061d7e23f2143eca8199a10dfd53f99
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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