Cesium fluoride → Tert-butyl 4-[4-[6-amino-5-(6-fluorooxazolo[4,5-b]pyridin-2-yl)-3-pyridyl]pyrazol-1-yl]piperidine-1-carboxylate

HRID 908416Notes

Reaction equation

HRID 908416 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.Br[C:29]1[CH:30]=[C:31]([C:36]2[O:37][C:38]3[C:39]([N:45]=2)=[N:40][CH:41]=[C:42]([F:44])[CH:43]=3)[C:32]([NH2:35])=[N:33][CH:34]=1.[F-].[Cs+]>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CO>[NH2:35][C:32]1[N:33]=[CH:34][C:29]([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:30][C:31]=1[C:36]1[O:37][C:38]2[C:39]([N:45]=1)=[N:40][CH:41]=[C:42]([F:44])[CH:43]=2

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 67388498HCID 67388498, compound

Product 1

HCID 67389039Tert-butyl 4-[4-[6-amino-5-(6-fluorooxazolo[4,5-b]pyridin-2-yl)-3-pyridyl]pyrazol-1-yl]piperidine-1-carboxylateYield 87.5%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

Tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]piperidine-1-carboxylate (222 mg) and 5-bromo-3-(6-fluorooxazolo[4,5-b]pyridin-2-yl)pyridin-2-amine (140 mg), bis(triphenylphosphine) palladium (II) chloride (15.9 mg) and caesium fluoride (172 mg) were weighed out in a microwave vial and sealed. Methanol (2 ml) was added and nitrogen was bubbled in the resulting suspension. The resulting mixture was heated in a 300 W microwave at 120° C. for 20 minutes. The crude product was purified by flash chromatography on silica gel (dried deposit with silica gel) eluting with 0 to 5% methanol in dichloromethane. The solvent was evaporated to dryness to afford tert-butyl 4-[4-[6-amino-5-(6-fluorooxazolo[4,5-b]pyridin-2-yl)-3-pyridyl]pyrazol-1-yl]piperidine-1-carboxylate (190 mg). NMR Spectrum: (CDCl3) 1.49 (s, 9H), 1.94-2.03 (m, 2H), 2.16-2.24 (m, 2H), 2.84-3.00 (m, 2H), 3.28 (bs, 2H), 3.29-3.37 (m, 1H), 6.94 (bs, 2H), 7.66 (dd, 1H), 7.68 (s, 1H), 7.79 (s, 1H), 8.35 (d, 1H), 8.45 (d, 1H), 8.48 (dd, 1H); Mass spectrum: M+H+ 480.

Workup

  1. customsealed
  2. customnitrogen was bubbled in the resulting suspension
  3. customThe crude product was purified by flash chromatography on silica gel (dried deposit with silica gel)
  4. washeluting with 0 to 5% methanol in dichloromethane
  5. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-efe8c8345f404801824827897ecf7bb8
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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