Sodium Carbonate → HCID 178432609, compound

HRID 1530630Notes

Reaction equation

HRID 1530630 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([CH3:19])[C:6]=1[CH:7]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8]1.[CH3:20][C:21]1[N:25]=[C:24]([C:26]2[N:27]=[C:28]3[N:38]([CH:39]=2)[CH2:37][CH2:36][O:35][C:34]2[C:29]3=[CH:30][CH:31]=[C:32](B3OC(C)(C)C(C)(C)O3)[CH:33]=2)[N:23]([CH:49]([CH3:51])[CH3:50])[N:22]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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:15]([O:14]1[CH2:8][CH:7]([C:6]2[N:5]([CH3:19])[N:4]=[CH:3][C:2]=2[C:32]2[CH:33]=[C:34]3[C:29](=[CH:30][CH:31]=2)[C:28]2[N:38]([CH:39]=[C:26]([C:24]4[N:23]([CH:49]([CH3:50])[CH3:51])[N:22]=[C:21]([CH3:20])[N:25]=4)[N:27]=2)[CH2:37][CH2:36][O:35]3)[CH2:11][CH2:10][NH:9][C:12]1=[O:13])([CH3:18])([CH3:17])[CH3:16]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 582043852-(2-Isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azuleneHCID 68313064tert-butyl 3-(4-bromo-1-methyl-1H-pyrazol-5-yl)pyrrolidine-1-carboxylate

Product 1

HCID 178432609HCID 178432609, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl 3-(4-bromo-1-methyl-1H-pyrazol-5-yl)pyrrolidine-1-carboxylate (1.0 g, 3.1 mmol), 4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-12-(tetramethyl-1,3,2-dioxaborolan-2-yl)-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1 (14),2,4,10,12-pentaene (1.1 g, 2.5 mmol), Pd(dppf)Cl2 (310 mg, 0.379 mmol), and Na2CO3 (1.34 g, 12.6 mmol) in dioxane (20 mL) was stirred at 80° C. for 16 h. The resultant mixture was extracted with ethyl acetate (50 mL), washed with brine, dried over MgSO4, filtered, and evaporated to afford the crude product, which was purified by reverse phase Combiflash eluting with a 0-70% gradient of CH3CN in 0.3% NH4HCO3 to give 1-tert-butyl-6-(1-methyl-4-{4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaen-12-yl}-1H-pyrazol-5-yl)-λ3,3-oxazepan-2-one (920 mg, 46% yield) as white solid. LCMS (ESI) m/z: 559.4 [M+H+]. 1H-NMR (500 MHz, DMSO-d6) δ 8.41 (d, J=8.5 Hz, 1H), 7.91 (s, 1H), 7.48 (s, 1H), 7.09 (d, J=8.5 Hz, 1H), 6.96 (s, 1H), 5.88-5.85 (m, 1H), 4.53 (s, 4H), 3.75 (s, 3H), 3.72 (s, 1H), 3.60 (s, 1H), 3.51-3.42 (m, 2H), 3.24-3.20 (m, 1H), 2.26 (s, 3H), 2.15-2.07 (m, 2H), 1.46 (s, 6H), 1.37 (s, 9H).

Workup

  1. extractionThe resultant mixture was extracted with ethyl acetate (50 mL)
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customto afford the crude product, which
  7. customwas purified by reverse phase Combiflash
  8. washeluting with a 0-70% gradient of CH3CN in 0.3% NH4HCO3

Sources & evidence

ORD record
ord-13f5d3b2f1aa4f6eaa742a7e52356ebb
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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