N-tert-Butylglycine → HCID 59249496, compound

HRID 1807105Notes

Reaction equation

HRID 1807105 reaction equation
[CH3:1][C:2]([O:41][CH2:42][C@@H:43]1[CH2:45][O:44]1)([CH3:40])[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([CH:12]2[CH:16]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=3[F:24])[C:15]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=3[F:34])([C:25]#[N:26])[CH:14]([CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[NH:13]2)=[O:11])=[N:5]1.C([NH:50][CH2:51][C:52]([OH:54])=[O:53])(C)(C)C>C(O)(C)C>[Cl:23][C:19]1[C:18]([F:24])=[C:17]([C@@H:16]2[C@:15]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=3[F:34])([C:25]#[N:26])[C@H:14]([CH2:35][C:36]([CH3:38])([CH3:37])[CH3:39])[NH:13][C@H:12]2[C:10]([NH:9][C:6]2[CH:7]=[CH:8][N:4]([CH2:3][C:2]([CH3:1])([CH3:40])[O:41][CH2:42][C@@H:43]([OH:44])[CH2:45][NH:50][CH2:51][C:52]([OH:54])=[O:53])[N:5]=2)=[O:11])[CH:22]=[CH:21][CH:20]=1

Participants

4

Reactant 2

HCID 414246N-tert-ButylglycineHCID 86640463HCID 86640463, compound

Product 1

HCID 59249496HCID 59249496, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethylpropyl)-pyrrolidine-2-carboxylic acid {1-[2-methyl-2-((S)-1-oxiranylmethoxy)-propyl]-1H-pyrazol-3-yl}-amide (85.8 mg, 0.133 mmol), isopropyl alcohol (2 mL), and t-butyl glycine (35 mg, 0.266 mmol) was microwaved at 130° C. for 15 min. The solvent evaporated under reduced pressure. The resulting oil was dissolved in dichloromethane (2 mL) and cooled to 0° C.; then TFA (1 mL) was slowly added and stirred for 4 h. The mixture was concentrated under reduced pressure and purified by reverse phase chromatography (20-95% of ACN/water) to give rac-{(S)-3-[2-(3-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-pyrazol-1-yl)-1,1-dimethyl-ethoxy]-2-hydroxy-propylamino}-acetic acid (18.1 mg, 19%) as an off-white powder. HRMS (ES+) m/z Calcd for C35H42Cl2F2N6O5S+H [(M+H)+]: 735.2635. found: 735.2631

Workup

  1. customwas microwaved at 130° C. for 15 min
  2. customThe solvent evaporated under reduced pressure
  3. dissolutionThe resulting oil was dissolved in dichloromethane (2 mL)
  4. additionthen TFA (1 mL) was slowly added
  5. concentrationThe mixture was concentrated under reduced pressure
  6. custompurified by reverse phase chromatography (20-95% of ACN/water)

Sources & evidence

ORD record
ord-c4496bab5f00496798effb8f3ccebfae
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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