Hydrochloric Acid → HCID 58438624, compound

HRID 1898615Notes

Reaction equation

HRID 1898615 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:31])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19](Br)[N:20]=3)[N:15]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2].[C:32]([C:35]1[CH:36]=[C:37](B(O)O)[CH:38]=[CH:39][CH:40]=1)([OH:34])=[O:33].C([O-])([O-])=O.[Na+].[Na+].Cl>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]([CH:3]1[CH2:6][N:5]([C:7](=[O:31])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:39]4[CH:40]=[C:35]([CH:36]=[CH:37][CH:38]=4)[C:32]([OH:34])=[O:33])[N:20]=3)[N:15]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 27339573-Carboxyphenylboronic acidHCID 584386122-Bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]amide

Product 1

HCID 58438624HCID 58438624, compoundYield 67.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (200 mg, 0.39 mmol) (approx 3:1 mix of 5-Br & 5-Cl) and 3-carboxyphenylboronic acid (85.0 mg, 0.51 mmol) in 1,2-DME (4 mL) were added Pd(Ph3P)4 (22.8 mg, 0.02 mmol) and 2.0 M aqueous Na2CO3 (0.8 mL, 1.6 mmol). The reaction mixture was heated at 90° C. overnight then cooled to room temp and diluted with water. The pH was adjusted to 6 with 1.0 M HCl before extracting with EtOAc (2×). The combined organics were dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography (0% to 4% MeOH/CH2Cl2 (0.5% NH4OH)) to afford 145 mg (67%) of 3-[7-[(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethylcarbamoyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-benzoic acid as a white foamy solid.

Workup

  1. temperaturethen cooled to room temp
  2. extractionbefore extracting with EtOAc (2×)
  3. dry with materialThe combined organics were dried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography (0% to 4% MeOH/CH2Cl2 (0.5% NH4OH))

Sources & evidence

ORD record
ord-bf828acc254347188a9348462aa939ec
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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