Sodium Carbonate → HCID 86727506, compound

HRID 519121Notes

Reaction equation

HRID 519121 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([C@H:13]([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[C@H:19]([CH3:31])[C:20](=[O:30])[NH:21][N:22]=2)[CH3:14])([CH3:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>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[CH2:11][C:10]([C@@H:13]([C:15]2[CH:16]=[C:17]3[C:26](=[CH:27][C:28]=2[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=2[F:32])[O:25][CH2:24][C:23]2[N:18]3[C@H:19]([CH3:31])[C:20](=[O:30])[NH:21][N:22]=2)[CH3:14])([CH3:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343542-Fluorophenylboronic acidHCID 86727499HCID 86727499, compound

Product 1

HCID 86727506HCID 86727506, compoundYield 100.7%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

To a solution of 3-[(S)-1-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl)-ethyl]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (Example #133, Step D, 0.08 g, 0.162 mmol), (2-fluorophenyl)boronic acid (0.027 g, 0.195 mmol) and sodium carbonate (0.034 g, 0.324 mmol) in 1,4-dioxane (2.0 mL) and water (0.5 mL) was added PdCl2(dppf)-DCM adduct (0.013 g, 0.016 mmol) and the reaction mixture was stirred at 90° C. overnight. The reaction mixture was cooled to ambient temperature and filtered. The filtrate was partitioned between EtOAc (30 mL) and water (30 mL). The organic layer was separated and the aqueous phase was extracted with EtOAc (3×50 mL). The combined organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated in vacuo and the residue was purified by prep-TLC (eluting with 5% methanol in dichloromethane) to give 3-{(R)-1-[(R)-7-(2-fluoro-phenyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-ethyl}-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (0.083 g, 100%). 1H NMR (CDCl3, 400 MHz): δ 8.12 (br. s, 1H), 7.37 (m, 1H), 7.08-7.26 (m, 3H), 6.84-6.91 (m, 1H), 6.79 (m, 1H), 4.73-4.87 (m, 1H), 4.59-4.68 (m, 2H), 3.57 (m, 1H), 3.44-3.51 (m, 1H), 3.33-3.41 (m, 1H), 3.25 (m, 1H), 2.86 (m, 1H), 1.55 (d, J=6.8 Hz, 3H), 1.35-1.47 (m, 9H), 1.22-1.35 (m, 3H), 1.07-1.21 (m, 3H). LC/MS (Table 1, Method 25) Rt=0.883 min; MS (ESI): m/z 531 [M+Na]+ and 453 [M+H−56]+.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. filtrationfiltered
  3. customThe filtrate was partitioned between EtOAc (30 mL) and water (30 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous phase was extracted with EtOAc (3×50 mL)
  6. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customThe filtrate was evaporated in vacuo
  9. customthe residue was purified by prep-TLC (eluting with 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-0d1d8dd5506f485d967e9bb10b4159e4
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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