Potassium Carbonate → HCID 68514091, compound

HRID 2241363Notes

Reaction equation

HRID 2241363 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:28][C:29]([C:31]2[C:32](=[O:44])[N:33]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)[N:34]=[CH:35][CH:36]=2)=[O:30])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[N:15]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[N:16]=[C:17](I)[C:10]=12.[CH3:45][N:46]([CH:54]1[CH2:59][CH2:58][NH:57][CH2:56][CH2:55]1)[C:47](=[O:53])[O:48][C:49]([CH3:52])([CH3:51])[CH3:50].N1CCC[C@H]1C(O)=O.C([O-])([O-])=O.[K+].[K+]>[Cu]I.CS(C)=O>[F:1][C:2]1[CH:3]=[C:4]([NH:28][C:29]([C:31]2[C:32](=[O:44])[N:33]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)[N:34]=[CH:35][CH:36]=2)=[O:30])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[N:15]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[N:16]=[C:17]([N:57]3[CH2:56][CH2:55][CH:54]([N:46]([CH3:45])[C:47](=[O:53])[O:48][C:49]([CH3:50])([CH3:51])[CH3:52])[CH2:59][CH2:58]3)[C:10]=12

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 27568064-N-Boc-4-N-Methyl-aminopiperidineHCID 68513145HCID 68513145, compound

Product 1

HCID 68514091HCID 68514091, compoundYield 87.8%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A round-bottomed flask was charged with N-(4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (100 mg, 0.142 mmol, prepared in Example 63, step A), tert-butyl methyl(piperidin-4-yl)carbamate (152 mg, 0.708 mmol), copper(I)iodide (5.39 mg, 0.0283 mmol), (S)-pyrrolidine-2-carboxylic acid (6.52 mg, 0.0566 mmol), K2CO3 (97.8 mg, 0.708 mmol) and DMSO (10 mL). The reaction mixture was stirred at 100° C. overnight. The reaction was cooled to ambient temperature and partitioned between EtOAc and H2O. The phases were separated and the aqueous phase was re-extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1, v/v) to afford product (98.5 mg, 87.8%). LRMS (APCI pos): m/e 693 (M−99).

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. custompartitioned between EtOAc and H2O
  3. customThe phases were separated
  4. extractionthe aqueous phase was re-extracted with EtOAc
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a crude product
  9. customThe crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1

Sources & evidence

ORD record
ord-ccc0a57a40a24be985cde721003b738f
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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