Hydrochloric Acid → (R)-3-((2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-4,4-dimethylpentanoic acid

HRID 1055099Notes

Reaction equation

HRID 1055099 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15](S(C)=O)[CH:14]=[CH:13][N:12]=3)=[CH:9][N:8]([S:20]([C:23]3[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:5]2=[N:6][CH:7]=1.[NH2:30][C@@H:31]([C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:32][C:33]([OH:35])=[O:34].C([O-])([O-])=O.[Na+].[Na+].Cl>C1COCC1.C(#N)C>[F:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:30][C@@H:31]([C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:32][C:33]([OH:35])=[O:34])[CH:14]=[CH:13][N:12]=3)=[CH:9][N:8]([S:20]([C:23]3[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 7010080(R)-3-Amino-4,4-dimethylpentanoic acidHCID 712472875-fluoro-3-(4-(methylsulfinyl)pyrimidin-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 71247748(R)-3-((2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-4,4-dimethylpentanoic acidYield 31%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 5-fluoro-3-(4-(methylsulfinyl)pyrimidin-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine, 127a, (0.052 g, 0.121 mmol) and (3R)-3-amino-4,4-dimethyl-pentanoic acid, 2a, (0.035 g, 0.242 mmol) along with Na2CO3 (0.051 g, 0.483 mmol) in a mixture of THF (0.780 mL) and acetonitrile (0.260 mL) was heated to 125° C. for 30 minutes under microwave irradiation. Then, the temperature was raised to 150° C. for a further 2.5 hours. The mixture was neutralized with aqueous 2N HCl and extracted with several portions of EtOAc. The organic solvents were evaporated in vacuo. Purification by flash chromatography (SiO2, 0-100% hexanes-EtOAc (with 10% MeOH)) provided 19 mg of the desired material (31% yield), which was used in the next step without further purification: LCMS Gradient 10-90%, 0.1% trifluoroacetic acid, 5 minutes, C18/ACN, RT=2.70 minutes (M+H) 512.00.

Workup

  1. temperatureThen, the temperature was raised to 150° C. for a further 2.5 hours
  2. extractionextracted with several portions of EtOAc
  3. customThe organic solvents were evaporated in vacuo
  4. customPurification by flash chromatography (SiO2, 0-100% hexanes-EtOAc (with 10% MeOH))

Sources & evidence

ORD record
ord-3632324491164d6abf13c13f95712cd3
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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