Trifluoroacetic acid → (1R*,2S*)-(E)-1'-methyl-2-(3-(4-(piperazin-1-yl)styryl)-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-one 2,2,2-trifluoroacetate

HRID 447399Notes

Reaction equation

HRID 447399 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C@H:11]3[C@@:13]4([C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[N:15]([CH3:22])[C:14]4=[O:23])[CH2:12]3)=[CH:8][CH:9]=2)[NH:4][N:3]=1.CC1(C)C(C)(C)OB(/[CH:32]=[CH:33]/[C:34]2[CH:39]=[CH:38][C:37]([N:40]3[CH2:45][CH2:44][N:43](C(OC(C)(C)C)=O)[CH2:42][CH2:41]3)=[CH:36][CH:35]=2)O1.[C:54]([OH:60])([C:56]([F:59])([F:58])[F:57])=[O:55]>C(Cl)Cl>[F:57][C:56]([F:59])([F:58])[C:54]([OH:60])=[O:55].[CH3:22][N:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[C@:13]2([CH2:12][C@H:11]2[C:7]2[CH:6]=[C:5]3[C:10]([C:2](/[CH:32]=[CH:33]/[C:34]4[CH:35]=[CH:36][C:37]([N:40]5[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]5)=[CH:38][CH:39]=4)=[N:3][NH:4]3)=[CH:9][CH:8]=2)[C:14]1=[O:23]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 66734336(E)-tert-butyl 4-(4-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)phenyl)piperazine-1-carboxylateHCID 178481340HCID 178481340, compound

Product 1

HCID 67955041(1R*,2S*)-(E)-1'-methyl-2-(3-(4-(piperazin-1-yl)styryl)-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-one 2,2,2-trifluoroacetateYield 4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The title compound was synthesized according to the method of Example A45, except substituting (1R*,2S*)-2-(3-iodo-1H-indazol-6-yl)-1′-methylspiro[cyclopropane-1,3′-indolin]-2′-one (37 mg, 0.090 mmol) and (E)-tert-butyl 4-(4-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)phenyl)piperazine-1-carboxylate (45 mg, 0.109 mmol). The solvent was removed and the Boc-protected amine purified by column chromatography (silica gel, CH2Cl2/MeOH, 95:5) to give an impure product which dissolved into CH2Cl2 (2.0 mL) and TFA (200 uL) was added. The reaction was stirred for 2 h, the solvent removed and the residue purified by prep-HPLC to give the title compound as an off-white powder (2.0 mg, 4.0%); 1H NMR (400 MHz, CD3OD) δ 7.97 (d, J=8.5 Hz, 1H), 7.56 (d, J=8.4 Hz, 2H), 7.46-7.41 (m, 2H), 7.30 (d, J=17 Hz, 1H), 7.15 (t, J=7.2 Hz, 1H), 7.06-6.99 (m, 4H), 6.65 (t, J=8.0 Hz, 1H), 6.02 (d, J=7.7 Hz, 1H), 3.49-3.44 (m, 4H), 3.40-3.31 (m, 8H), 2.28-2.25 (m, 1H), 2.21-2.18 (m, 1H); MS ESI [M+H]+ 476.2, calcd for [C30H29N5O+H]+ 476.25.

Workup

  1. customThe title compound was synthesized
  2. customThe solvent was removed
  3. customthe Boc-protected amine purified by column chromatography (silica gel, CH2Cl2/MeOH, 95:5)
  4. customto give an impure product which
  5. additionwas added
  6. customthe solvent removed
  7. customthe residue purified by prep-HPLC

Sources & evidence

ORD record
ord-57620e803f304e48902edfe513406620
Source dataset
uspto-grants-2013_07
Patent number
US08481533B2

Reaction notes

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