Sodium Carbonate → HCID 71286171, compound

HRID 1752445Notes

Reaction equation

HRID 1752445 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=3)=[CH:11][CH:10]=2)O1.[NH2:28][C:29](=[O:43])[C@@H:30]([NH:32][C:33]1[N:38]=[C:37](Cl)[N:36]=[C:35]([C:40]([NH2:42])=[O:41])[CH:34]=1)[CH3:31].C([O-])([O-])=O.[Na+].[Na+]>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.O1CCOCC1>[NH2:28][C:29](=[O:43])[C@@H:30]([NH:32][C:33]1[N:38]=[C:37]([C:9]2[CH:10]=[CH:11][C:12]([O:15][C:16]3[CH:17]=[CH:18][C:19]([O:22][C:23]([F:24])([F:25])[F:26])=[CH:20][CH:21]=3)=[CH:13][CH:14]=2)[N:36]=[C:35]([C:40]([NH2:42])=[O:41])[CH:34]=1)[CH3:31]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 71285887HCID 71285887, compoundHCID 89422280HCID 89422280, compound

Product 1

HCID 71286171HCID 71286171, compoundYield 31.3%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
10 °C

Procedure

A 50-mL vial with a screw-top septum was charged with 200 mg of 4,4,5,5-tetramethyl-2-(4-(4-(trifluoromethoxy)phenoxy)phenyl)-1,3,2-dioxaborolane, 1 equivalent (S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-chloropyrimidine-4-carboxamide (129 mg, 0.53 mmol), 1.5 mL 2M aqueous Na2CO3, 0.07 equivalents PdCl2(PPh3)2 (28 mg, 0.04 mmol), and 8 mL dioxane. The vial was purged with nitrogen and heated to 10° C. for 6 h, at which time the reaction was complete. The mixture was diluted with 100 mL EtOAc and washed two times with 100 mL water. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was chromatographed by combiflash using a 40-gram silica column with a gradient EtOAc (100% max) in hexane to provide 76 mg (31% yield) of (S)-6-((1-amino-1-oxopropan-2-yl)amino)-2-(4-(4-(trifluoromethoxy)phenoxy)phenyl)pyrimidine-4-carboxamide as a white solid. m/z 461, 1H NMR (CD3OD): 8.56-8.49 (m, 2H), 7.35-7.27 (m, 2H), 7.17-7.11 (m, 3H), 7.09-7.02 (m, 2H), 4.64-4.49 (m, 1H), 4.56-1.49 (m, 3H).

Workup

  1. customThe vial was purged with nitrogen
  2. additionThe mixture was diluted with 100 mL EtOAc
  3. washwashed two times with 100 mL water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was chromatographed by combiflash

Sources & evidence

ORD record
ord-ce7006f5c7a14541929ab3b8310aa74a
Source dataset
uspto-grants-2015_10
Patent number
US09163008B2

Reaction notes

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