Sodium Bicarbonate → HCID 86727158, compound

HRID 579337Notes

Reaction equation

HRID 579337 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)O1.Br[C:16]1[CH:21]=[C:20]([O:22][CH3:23])[C:19]([C:24]2[S:28][C:27]([N:29]([CH3:40])[CH:30]3[CH2:35][C:34]([CH3:37])([CH3:36])[NH:33][C:32]([CH3:39])([CH3:38])[CH2:31]3)=[N:26][N:25]=2)=[C:18]([F:41])[CH:17]=1.C([O-])(O)=O.[Na+]>O1CCOCC1.O.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>[F:41][C:18]1[CH:17]=[C:16]([C:9]2[CH:13]=[N:12][NH:11][CH:10]=2)[CH:21]=[C:20]([O:22][CH3:23])[C:19]=1[C:24]1[S:28][C:27]([N:29]([CH3:40])[CH:30]2[CH2:35][C:34]([CH3:36])([CH3:37])[NH:33][C:32]([CH3:39])([CH3:38])[CH2:31]2)=[N:26][N:25]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86727159HCID 86727159, compound

Product 1

HCID 86727158HCID 86727158, compoundYield 32%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Pd(Ph3P)4 (11 mg, 0.009 mmol) was added to a stirred suspension of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (55 mg, 0.282 mmol) and 5-(4-bromo-2-fluoro-6-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (86 mg, 0.188 mmol) in dioxane (1.5 mL), followed by a solution of NaHCO3 (60 mg, 0.564 mmol) in water (0.375 mL). The reaction mixture was purged with nitrogen, sealed, and heated at 120° C. under microwave irradiation for 1 hour. The reaction mixture was diluted with DCM (20 mL) and washed with saturated NaHCO3(aq) (10 mL). The organic phase was separated and SiliaMetS-DMT (0.61 mmol/g, 145 mg, 0.09 mmol) was added. The resulting suspension was stirred at room temperature for ˜2 hours then filtered. The filtrate was concentrated in vacuo to afford the crude product as a light brown oil. The crude material was purified by UV directed preparative HPLC under basic conditions (NH4OH modified), collecting at 328 nm to afford the title compound as a white solid (26 mg, 32% yield). LC-MS: Rt 0.76 min; MS m/z 445.5 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.09 (br. s., 1H), 8.26 (br. s., 2H), 7.23-7.31 (m, 2H), 4.27-4.37 (m, 1H), 3.93 (s, 3H), 2.98 (s, 3H), 1.62 (dd, J=11.87, 3.28 Hz, 2H), 1.42 (t, J=12.13 Hz, 2H), 1.20 (s, 6H), 1.09 (s, 6H).

Workup

  1. customThe reaction mixture was purged with nitrogen
  2. customsealed
  3. additionThe reaction mixture was diluted with DCM (20 mL)
  4. washwashed with saturated NaHCO3(aq) (10 mL)
  5. customThe organic phase was separated
  6. additionSiliaMetS-DMT (0.61 mmol/g, 145 mg, 0.09 mmol) was added
  7. filtrationthen filtered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customto afford the crude product as a light brown oil
  10. customThe crude material was purified by UV
  11. customcollecting at 328 nm

Sources & evidence

ORD record
ord-be0da0b6e56f47c8b89b21d5f5a9cb60
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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