Sodium Carbonate → HCID 86727167, compound

HRID 579344Notes

Reaction equation

HRID 579344 reaction equation
Br[C:2]1[S:6][C:5]([N:7]([CH3:18])[CH:8]2[CH2:13][C:12]([CH3:15])([CH3:14])[NH:11][C:10]([CH3:17])([CH3:16])[CH2:9]2)=[N:4][N:3]=1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[C:22]([O:29][CH3:30])[CH:21]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.CCOC(C)=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>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([C:2]2[S:6][C:5]([N:7]([CH3:18])[CH:8]3[CH2:13][C:12]([CH3:15])([CH3:14])[NH:11][C:10]([CH3:17])([CH3:16])[CH2:9]3)=[N:4][N:3]=2)=[C:22]([O:29][CH3:30])[CH:21]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 3858606(4-Chloro-2-methoxyphenyl)boronic acidHCID 867271295-Bromo-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine2×

Product 1

HCID 86727167HCID 86727167, compoundYield 89%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Nitrogen was bubbled through a stirred solution of 5-bromo-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine [Intermediate 4] (1 g, 3.00 mmol) and (4-chloro-2-methoxyphenyl)boronic acid (0.615 g, 3.30 mmol) in dioxane (20 mL). To this mixture was added Pd(PPh3)4 (0.173 g, 0.150 mmol) followed by a solution of Na2CO3 (0.954 g, 9.00 mmol) in water (5 mL). The reaction was heated at 80° C. for 18 hours. The reaction mixture was cooled to RT, diluted with EtOAc (150 mL) and washed with water (100 mL). The organic phase was separated, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo to afford the crude product as a dark red/brown oil which solidified on standing. The crude material was purified by flash chromatography using an 80 g silica cartridge running a gradient of [2M NH3 in MeOH]/DCM to afford the title compound as an off-white solid (1.051 g, 89% yield). LC-MS: Rt 1.04 min; MS m/z 395.2 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.09 (d, J=8.59 Hz, 1H), 7.32 (d, J=2.02 Hz, 1H), 7.15 (dd, J=8.59, 2.02 Hz, 1H), 4.35 (tt, J=12.38, 3.54 Hz, 1H), 3.97 (s, 3H), 2.98 (s, 3H), 1.60 (dd, J=11.87, 3.28 Hz, 2H), 1.41 (t, J=12.13 Hz, 2H), 1.27 (s, 1H), 1.21 (s, 6H), 1.08 (s, 6H).

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. washwashed with water (100 mL)
  3. customThe organic phase was separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customto afford the crude product as a dark red/brown oil which
  8. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-3ed232942d6e4664b6cc73d7cf7902de
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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