Hydrochloric Acid → HCID 86727148, compound

HRID 579327Notes

Reaction equation

HRID 579327 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.[CH3:19][O:20][C:21]1[CH:30]=[C:29]2[C:24]([CH:25]=[CH:26][CH:27]=[N:28]2)=[CH:23][C:22]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].Cl.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.C(COC)OC.O>[CH3:19][O:20][C:21]1[CH:30]=[C:29]2[C:24]([CH:25]=[CH:26][CH:27]=[N:28]2)=[CH:23][C:22]=1[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

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 867271295-Bromo-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine2×HCID 86727149(7-Methoxyquinolin-6-yl)boronic acid

Product 1

HCID 86727148HCID 86727148, compoundYield 84.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

In a microwave tube, a mixture of 5-bromo-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (Intermediate 4) (100 mg, 0.300 mmol), (7-methoxyquinolin-6-yl)boronic acid (˜50% by weight, 171 mg, 0.420 mmol) and sodium carbonate (95 mg, 0.90 mmol) in 3:1 dimethoxyethane/water (2.5 mL) was degassed with a dry stream of nitrogen for five minutes. Tetrakis(triphenylphosphine)palladium(0) (34.7 mg, 0.030 mmol) was added and the mixture heated in a microwave at 140° C. for 30 min. The mixture was diluted with water and extracted with DCM (6×). HCl in dioxane (1 M, 1.2 mL, 1.2 mmol) was added and the solution concentrated to dryness. SCX purification (2 g column, 7 M ammonia in MeOH elution) provided a brown residue which was further purified by flash column chromatography (12 g silica gel, 1-17% 1.4 N ammonia in MeOH gradient in DCM over 30 column volumes) to provide 5-(7-methoxyquinolin-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine as a yellow solid (104 mg, 84%). MS=412.3 (M+1), Rt=0.45 min [Method D]. 1H NMR (400 MHz, METHANOL-d4) ppm 8.83 (dd, J=4.3, 1.8 Hz, 1H), 8.71 (s, 1H), 8.42 (d, J=8.1 Hz, 1H), 7.57 (s, 1H), 7.48 (dd, J=8.3, 4.3 Hz, 1H), 4.43-4.57 (m, 1H), 4.16 (s, 3H), 3.11 (s, 3H), 1.81 (dd, J=12.6, 3.0 Hz, 2H), 1.58 (t, J=12.4 Hz, 2H), 1.37 (s, 6H), 1.25 (s, 6H).

Workup

  1. customwas degassed with a dry stream of nitrogen for five minutes
  2. extractionextracted with DCM (6×)
  3. concentrationthe solution concentrated to dryness
  4. customSCX purification (2 g column, 7 M ammonia in MeOH elution)
  5. customprovided a brown residue which
  6. customwas further purified by flash column chromatography (12 g silica gel, 1-17% 1.4 N ammonia in MeOH gradient in DCM over 30 column volumes)

Sources & evidence

ORD record
ord-1d8c6a10651041e4ab6204252e705773
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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