Cesium fluoride → HCID 67388157, compound

HRID 908487Notes

Reaction equation

HRID 908487 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][N:12]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[CH:13]=2)O1.[NH2:28][C:29]1[C:34]([C:35]2[O:36][C:37]3[C:43]([C:44]([O:46][CH3:47])=[O:45])=[CH:42][CH:41]=[CH:40][C:38]=3[N:39]=2)=[CH:33][C:32](Br)=[CH:31][N:30]=1.[F-].[Cs+]>CO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:28][C:29]1[C:34]([C:35]2[O:36][C:37]3[C:43]([C:44]([O:46][CH3:47])=[O:45])=[CH:42][CH:41]=[CH:40][C:38]=3[N:39]=2)=[CH:33][C:32]([C:9]2[CH:10]=[N:11][N:12]([CH:14]3[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:18][CH2:19]3)[CH:13]=2)=[CH:31][N:30]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 67388746HCID 67388746, compound

Product 1

HCID 67388157HCID 67388157, compoundYield 69.9%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of bis(triphenylphosphine)palladium chloride (17.69 mg) was added to tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]piperidine-1-carboxylate (380 mg), methyl 2-(2-amino-5-bromo-3-pyridyl)-1,3-benzoxazole-7-carboxylate (390 mg) and caesium fluoride (459 mg) dissolved in degassed methanol (5 ml) under argon. The resulting slurry was heated at 120° C. in the microwave for 30 minutes. The mixture was adsorbed on silica gel. The crude product was purified by flash chromatography on silica gel eluting with 1 to 4% methanol in dichloromethane. The solvent was evaporated to dryness to afford methyl 2-[2-amino-5-[1-(1-tert-butoxycarbonyl-4-piperidyl)pyrazol-4-yl]-3-pyridyl]-1,3-benzoxazole-7-carboxylate (365 mg) as a pale yellow solid. NMR Spectrum: (CDCl3) 1.49 (s, 9H), 1.97 (dd, 1H), 2.02 (dd, 1H), 2.16-2.23 (m, 2H), 2.84-3.01 (m, 2H), 4.06 (s, 3H), 4.19-4.40 (m, 3H), 6.88 (bs, 2H), 7.44 (dd, 1H), 7.70 (s, 1H), 7.80 (s, 1H), 7.94 (dd, 1H), 8.01 (dd, 1H), 8.40 (d, 1H), 8.48 (d, 1H); Mass spectrum: M+H+ 519;

Workup

  1. customThe crude product was purified by flash chromatography on silica gel eluting with 1 to 4% methanol in dichloromethane
  2. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-920b444d046f48b9a54d0436768779f9
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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