Potassium Carbonate → HCID 86727566, compound

HRID 519165Notes

Reaction equation

HRID 519165 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10]([NH:14][C:15]2[CH:16]=[C:17]3[C:26](=[CH:27][C:28]=2Br)[O:25][CH2:24][C:23]2[N:18]3[CH:19]([CH3:31])[C:20](=[O:30])[NH:21][N:22]=2)([CH3:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[F:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1B(O)O>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10]([NH:14][C:15]2[CH:16]=[C:17]3[C:26](=[CH:27][C:28]=2[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[F:38])[O:25][CH2:24][C:23]2[N:18]3[CH:19]([CH3:31])[C:20](=[O:30])[NH:21][N:22]=2)([CH3:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27343542-Fluorophenylboronic acidHCID 86727567HCID 86727567, compound

Product 1

HCID 86727566HCID 86727566, compoundYield 93%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 3-(7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-3-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.230 g, 0.465 mmol), K2CO3 (0.129 g, 0.930 mmol), (2-fluorophenyl)boronic acid (0.098 g, 0.698 mmol) and PdCl2(dppf)-CH2Cl2 adduct (0.038 g, 0.047 mmol) in dioxane (4 mL) and water (0.66 mL) was heated at 90° C. for 14 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by prep-TLC (eluting with 10% EtOAc in petroleum ether) to give 3-[7-(2-fluoro-phenyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-3-methyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.220 g, 93%) as a pale solid. 1H-NMR (400 MHz, CDCl3) δ 8.09-8.00 (brs, 1H), 7.41-7.31 (m, 1H), 7.24-7.19 (m, 2H), 7.19-7.08 (m, 1H), 6.73 (s, 1H), 6.46 (s, 1H), 4.79-4.66 (m, 1H), 4.64-4.47 (m, 1H), 3.55-3.08 (m, 4H), 2.16-1.93 (m, 2H), 1.58-1.55 (m, 3H), 1.50-1.37 (m, 12H). LC/MS (Table 1, Method 25) Rt=0.895 min; MS m/z: 510 [M+1]+.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by prep-TLC (eluting with 10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-55d655dbcbd34563856531f5962bb360
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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