Diisopropylethylamine → HCID 68762062, compound

HRID 387604Notes

Reaction equation

HRID 387604 reaction equation
Cl.Cl.[Cl:3][C:4]1[C:5]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[C:6]2[CH:12]=[N:11][NH:10][C:7]2=[N:8][CH:9]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[C:52]([O:56][C:57]([N:59]1[CH2:63][CH2:62][CH2:61][C@H:60]1[C@H:64]([C:68]1[CH:73]=[CH:72][C:71]([Cl:74])=[CH:70][CH:69]=1)[C:65](O)=[O:66])=[O:58])([CH3:55])([CH3:54])[CH3:53]>C(Cl)Cl>[Cl:3][C:4]1[C:5]([N:13]2[CH2:14][CH2:15][N:16]([C:65](=[O:66])[C@H:64]([C@@H:60]3[CH2:61][CH2:62][CH2:63][N:59]3[C:57]([O:56][C:52]([CH3:54])([CH3:53])[CH3:55])=[O:58])[C:68]3[CH:73]=[CH:72][C:71]([Cl:74])=[CH:70][CH:69]=3)[CH2:17][CH2:18]2)=[C:6]2[CH:12]=[N:11][NH:10][C:7]2=[N:8][CH:9]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59564918(S)-2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acidHCID 68761356HCID 68761356, compound

Product 1

HCID 68762062HCID 68762062, compoundYield 82.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 5-chloro-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridine dihydrochloride (75 mg, 0.205 mmol), 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate (V) (“HATU”; 78.0 mg, 0.205 mmol), N-ethyl-N-isopropylpropan-2-amine (143 μL, 0.821 mmol), and (S)-2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acid (83.7 mg, 0.246 mmol, see Example C) in CH2Cl2 (5 mL) was stirred at room temperature for 1 hour. The solvent was removed, and the resulting residue was redissolved in EtOAc (20 mL) and washed with water. The organic phase was dried over MgSO4, filtered, and concentrated in vacuo. The crude obtained was purified by C-18 reverse phase column chromatography (Biotage C-18 12M+) using 10-90% CHsCN/water gradient on Biotage SP4 unit. The fractions containing the product were pooled, and the solvents were removed and evaporated from CH3CN (3×10 mL). The residue was transferred to a 25 mL round bottom flask using EtOAc (about 5 to about 10 mL). The residue was concentrated in vacuo and dried under high vacuum for 2 hours to provide (S)-tert-butyl 2-((S)-2-(4-(5-chloro-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)-1-(4-chlorophenyl)-2-oxoethyl)pyrrolidine-1-carboxylate (95 mg, 0.170 mmol, 82.7% yield) as a solid. LCMS (APCI+) m/z 459.1 [(M-Boc)+H]+.

Workup

  1. customThe solvent was removed
  2. dissolutionthe resulting residue was redissolved in EtOAc (20 mL)
  3. washwashed with water
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude obtained
  8. customwas purified by C-18 reverse phase column chromatography (Biotage C-18 12M+)
  9. additionThe fractions containing the product
  10. customthe solvents were removed
  11. customevaporated from CH3CN (3×10 mL)
  12. customThe residue was transferred to a 25 mL round bottom flask
  13. concentrationThe residue was concentrated in vacuo
  14. customdried under high vacuum for 2 hours

Sources & evidence

ORD record
ord-24b7492fa31343a0affdfe8d561a0500
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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