Potassium Phosphate, Tribasic → HCID 67439166, compound

HRID 1185364Notes

Reaction equation

HRID 1185364 reaction equation
[C:1]([CH:11]1[CH2:17][CH2:16][CH2:15][N:14]([C:18]2[N:22]([CH3:23])[N:21]=[CH:20][C:19]=2[NH:24][C:25]([C:27]2[N:28]=[C:29](Br)[S:30][C:31]=2[NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:26])[C@@H:13]([NH2:41])[CH2:12]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[CH:42]1([C:45]2[CH:46]=[C:47]([CH3:63])[C:48]([F:62])=[C:49](B3OC(=O)CN(C)CC(=O)O3)[CH:50]=2)[CH2:44][CH2:43]1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CO.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([CH:11]1[CH2:17][CH2:16][CH2:15][N:14]([C:18]2[N:22]([CH3:23])[N:21]=[CH:20][C:19]=2[NH:24][C:25]([C:27]2[N:28]=[C:29]([C:49]3[CH:50]=[C:45]([CH:42]4[CH2:43][CH2:44]4)[CH:46]=[C:47]([CH3:63])[C:48]=3[F:62])[S:30][C:31]=2[NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:26])[C@@H:13]([NH2:41])[CH2:12]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 58464728HCID 58464728, compoundHCID 67437974HCID 67437974, compound

Product 1

HCID 67439166HCID 67439166, compoundYield 57.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

In a microwave reaction vessel, (R)-tert-butyl 4-(5-(4-Cbz-aminoazepan-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-bromothiazol-5-ylcarbamate (130 mg, 0.2 mmol), 2-(5-cyclopropyl-2-fluoro-3-methylphenyl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione (167 mg, 0.55 mmol), S-Phos (13.2 mg, 0.032 mmol) and palladium acetate (3.6 mg, 0.016 mmol) were dissolved in 1,4-dioxane (4.0 mL). The cap was closed and the reaction vessel was vacuum purged with nitrogen three times. Potassium phosphate (3.0M aq., 0.27 mL, 0.81 mmol, degassed before use) was added and mixture was stirred at room temperature for 10 min before heated under microwave at 120° C. for 20 min. The mixture was diluted with methanol and filtered through a pad of Celite and washed with copious amount of methylene chloride. The filtrate was concentrated in vacuo and purified on flash chromatography (Isco Co.) eluted with 0 to 5% methanol in methylene chloride to give (R)-tert-butyl 4-(5-(4-Cbz-aminoazepan-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-(5-cyclopropyl-2-fluoro-3-methylphenyl)thiazol-5-ylcarbamate (82 mg, 57%).

Workup

  1. customThe cap was closed
  2. custompurged with nitrogen three times
  3. temperaturebefore heated under microwave at 120° C. for 20 min
  4. filtrationfiltered through a pad of Celite
  5. washwashed with copious amount of methylene chloride
  6. concentrationThe filtrate was concentrated in vacuo
  7. custompurified on flash chromatography (Isco Co.)
  8. washeluted with 0 to 5% methanol in methylene chloride

Sources & evidence

ORD record
ord-545379f3b3d84b2a8923168dab9ffebf
Source dataset
uspto-grants-2014_03
Patent number
US08669361B2

Reaction notes

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