Trifluoroacetic acid → 7-chloro-2-(2-(4-(piperidin-4-ylsulfonyl)phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)isoindolin-1-one TFA salt

HRID 627806Notes

Reaction equation

HRID 627806 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([C:12]1[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([S:27]([CH:30]5[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]5)(=[O:29])=[O:28])=[CH:23][CH:22]=4)[N:19]=3)[N:14](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH:13]=1)[CH2:7]2.C([SiH](CC)CC)C.[C:69]([OH:75])([C:71]([F:74])([F:73])[F:72])=[O:70]>C(Cl)Cl>[OH:75][C:69]([C:71]([F:74])([F:73])[F:72])=[O:70].[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([C:12]1[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[CH:22]=[CH:23][C:24]([S:27]([CH:30]5[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]5)(=[O:28])=[O:29])=[CH:25][CH:26]=4)[N:19]=3)[NH:14][CH:13]=1)[CH2:7]2

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 71143607Tert-butyl 4-[4-[7-(7-chloro-1-oxo-isoindolin-2-yl)-5-trityl-pyrrolo[2,3-b]pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylate

Product 1

HCID 866765097-chloro-2-(2-(4-(piperidin-4-ylsulfonyl)phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)isoindolin-1-one TFA saltYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-butyl 4-[4-[7-(7-chloro-1-oxo-isoindolin-2-yl)-5-trityl-pyrrolo[2,3-b]pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylate (186 mg, 0.2187 mmol) dissolved in DCM (2 mL) and triethylsilane (175 μL, 1.094 mmol) then TFA (0.3 mL) added under N2. Reaction mixture stirred overnight and residue azeotroped with DCM (×2) then purified by hplc. Product isolated as the TFA salt (80 mg, 59%); 1H NMR (400 MHz, DMSO) δ 1.72 (2H, brdq), 2.08 (2H, brd), 2.89 (2H, brq), 3.37 (2H, partly obsc brd), 3.63-3.70 (1H, partly obsc m), 5.49 (2H, s), 7.59 (1H, d), 7.70 (1H, t), 7.74 (1H, t), 7.99 (2H, d), 8.10-8.26 (1H, m), 8.55-8.58 (4H, m), 9.11 (1H, s), 12.42 (1H, d) ppm; MS (ES+) 508.0.

Workup

  1. customReaction mixture
  2. customresidue azeotroped with DCM (×2)
  3. customthen purified by hplc

Sources & evidence

ORD record
ord-cae4f346d6a24d74b0884e9fb2263371
Source dataset
uspto-grants-2016_04
Patent number
US09309250B2

Reaction notes

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