Water → 4-{4-[6-Amino-5-(5-chloro-8-fluoroisoquinolin-3-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1926258Notes

Reaction equation

HRID 1926258 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:34])=[C:23](B4OC(C)(C)C(C)(C)O4)[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:35][C:36]1[CH:45]=[CH:44][C:43]([F:46])=[C:42]2[C:37]=1[CH:38]=[C:39](OS(C(F)(F)F)(=O)=O)[N:40]=[CH:41]2.C([O-])([O-])=O.[Cs+].[Cs+].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>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:34])=[C:23]([C:39]4[N:40]=[CH:41][C:42]5[C:37]([CH:38]=4)=[C:36]([Cl:35])[CH:45]=[CH:44][C:43]=5[F:46])[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 962WaterHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 534879604-[4-[6-Amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-3-yl]pyrazol-1-yl]piperidine-1-carboxylic acid tert-butyl esterHCID 86633140Trifluoromethanesulfonic acid 5-chloro-8-fluoroisoquinolin-3-yl ester

Product 1

HCID 675207684-{4-[6-Amino-5-(5-chloro-8-fluoroisoquinolin-3-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

4-{4-[6-Amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (0.065 g, 0.14 mmol) (BB3), trifluoromethanesulfonic acid 5-chloro-8-fluoroisoquinolin-3-yl ester (0.040 g, 0.12 mmol), Cs2CO3 (75 mg, 0.23 mmol), and Pd(PPh3)4 (7 mg, 0.006 mmol) were placed in a sealable microwave tube, taken up in 1,4-dioxane (2 mL, 30 mmol) and H2O (0.54 mL, 30 mmol), flushed with nitrogen, sealed and heated in the microwave reactor at 100° C. for 30 minutes. The reaction mixture was diluted with EtOAc washed with water, brine, dried over Na2SO4, filtered and concentrated. The compound was purified by prep-TLC with 5% 7M NH3 in MeOH and DCM mixture yielding the title compound as pale yellow solid. MS (ES+): m/z=523.15/525.12 (100/40) [MH+]. HPLC: tR=3.03 min (ZQ2, polar—5 min).

Workup

  1. customsealed
  2. washwashed with water, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe compound was purified by prep-TLC with 5% 7M NH3 in MeOH and DCM mixture

Sources & evidence

ORD record
ord-923f549a5c0c43ff874e7d319b20e44b
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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