Trifluoroacetic acid → (1R*,2S*)-5'-methoxy-2-(3-(4-(piperidin-4-yl)phenyl)-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-one 2,2,2-trifluoroacetate

HRID 2383691Notes

Reaction equation

HRID 2383691 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[C@:6]12[CH2:14][C@H:13]1[C:15]1[CH:23]=[C:22]2[C:18]([C:19]([C:24]3[CH:29]=[CH:28][C:27]([CH:30]4[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][CH2:31]4)=[CH:26][CH:25]=3)=[N:20][NH:21]2)=[CH:17][CH:16]=1.[C:43]([OH:49])([C:45]([F:48])([F:47])[F:46])=[O:44]>C(Cl)Cl>[F:46][C:45]([F:48])([F:47])[C:43]([OH:49])=[O:44].[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[C@:6]12[CH2:14][C@H:13]1[C:15]1[CH:23]=[C:22]2[C:18]([C:19]([C:24]3[CH:29]=[CH:28][C:27]([CH:30]4[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]4)=[CH:26][CH:25]=3)=[N:20][NH:21]2)=[CH:17][CH:16]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67446826tert-butyl 4-(4-(6-((1R,2S)-5'-methoxy-2'-oxospiro[cyclopropane-1,3'-indolin]-2-yl)-1H-indazol-3-yl)phenyl)piperidine-1-carboxylate

Product 1

HCID 67954423(1R*,2S*)-5'-methoxy-2-(3-(4-(piperidin-4-yl)phenyl)-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-one 2,2,2-trifluoroacetateYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-(4-(6-((1R,2S)-5′-methoxy-2′-oxospiro[cyclopropane-1,3′-indoline]-2-yl)-1H-indazol-3-yl)phenyl)piperidine-1-carboxylate (102 mg, 0.181 mmol) in CH2Cl2 (5 mL) was added TFA (0.4 mL, 5.4 mmol). The resulting reaction mixture was stirred at rt for 2.5 h. The crude reaction mixture was concentrated under reduced pressure to dryness, and purified by preparative HPLC to give the title compound as a yellow solid (20 mg, 72%). 1H NMR (400 MHz, MeOD) δ 7.89 (d, J=8.2 Hz, 3H), 7.47 (s, 1H), 7.41 (d, J=8.2 Hz, 2H), 7.01 (d, J=8.6 Hz, 1H), 6.83 (d, J=8.4 Hz, 1H), 6.91 (dd, J=8.4, 2.4 Hz, 1H), 5.60 (d, J=2.3 Hz, 1H), 3.56-3.50 (m, 2H), 3.39-3.32 (m, 1H), 3.25 (s, 3H), 3.17 (t, J=11.9 Hz, 2H), 3.02-2.92 (m, 1H), 2.25-2.22 (m, 1H), 2.19-2.01 (m, 3H), 2.02-1.91 (m, 2H); MS ESI 465.3 [M+H]+, calcd for [C29H28N4O2+H]+465.22.

Workup

  1. customThe resulting reaction mixture
  2. customThe crude reaction mixture
  3. concentrationwas concentrated under reduced pressure to dryness
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-b6d9bbf1a2ba441a9315d787833ee321
Source dataset
uspto-grants-2012_09
Patent number
US08263596B2

Reaction notes

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