Trifluoroacetic acid → 2-(3-[2-(5-Ethyl-pyridin-2-yl)-vinyl]-1H-indazol-6-ylamino)-N-prop-2-ynyl-benzamide

HRID 1827465Notes

Reaction equation

HRID 1827465 reaction equation
[CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([CH:9]=[CH:10][C:11]2[C:19]3[C:14](=[CH:15][C:16]([NH:20][C:21]4[CH:29]=[CH:28][CH:27]=[CH:26][C:22]=4[C:23](O)=[O:24])=[CH:17][CH:18]=3)[NH:13][N:12]=2)=[N:7][CH:8]=1)[CH3:2].C(O)(C(F)(F)F)=O.[CH2:37]([NH2:40])[C:38]#[CH:39].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1(C)C=CC=CC=1.CN(C=O)C.C(Cl)Cl>[CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([CH:9]=[CH:10][C:11]2[C:19]3[C:14](=[CH:15][C:16]([NH:20][C:21]4[CH:29]=[CH:28][CH:27]=[CH:26][C:22]=4[C:23]([NH:40][CH2:37][C:38]#[CH:39])=[O:24])=[CH:17][CH:18]=3)[NH:13][N:12]=2)=[N:7][CH:8]=1)[CH3:2]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 239041PropargylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 693546052-{3-[2-(5-Ethyl-pyridin-2-yl)-vinyl]-1H-indazol-6-ylamino}-benzoic acid

Product 1

HCID 865944612-(3-[2-(5-Ethyl-pyridin-2-yl)-vinyl]-1H-indazol-6-ylamino)-N-prop-2-ynyl-benzamideYield 66%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To 2-{3-[2-(5-Ethyl-pyridin-2-yl)-vinyl]-1H-indazol-6-ylamino}-benzoic acid (49 mg, 0.105 mmol) was added 2 mL of a 90:10:1 mixture of CH2Cl2:TFA:TES. The reaction was stirred at reflux for 1 hour, and then diluted with toluene (20 mL). The solvent was removed by rotary evaporation to yield a thick oil. The oil was dissolved in DMF (1 mL) and to this solution was added TEA (0.072 mL, 0.52 mmol), propargyl amine (0.014 mL, 0.208 mmol), and HATU (59 mg, 0.156 mmol). The reaction was stirred for 3 hours, and then purified by preparatory HPLC to yield the desired product (29 mg, 66%). 1H NMR (CDCL3-d): δ 9.83 (1H, s), 8.63 (2H, s), 8.04 (2H, m), 7.68 (2H, s), 7.47 (1H, m), 7.32 (1H, d, J=1.51 Hz), 7.10 (1H, dd, J1=8.67 Hz, J2=1.88 Hz), 6.93 (1H, m), 6.07 (2H, dd, J1=5.09 Hz, J2=2.26 Hz), 3.15 (1H, t, J=2.35 Hz), 2.97 (2H, s), 2.74 (1H, s), 2.29 (1H, s), 1.27 (3H, t, J=7.44 Hz)

Workup

  1. temperatureat reflux for 1 hour
  2. customThe solvent was removed by rotary evaporation
  3. customto yield a thick oil
  4. stirringThe reaction was stirred for 3 hours
  5. custompurified by preparatory HPLC

Sources & evidence

ORD record
ord-629052a5ffb144d8a4eb4ccf082627c3
Source dataset
uspto-grants-2006_05
Patent number
US07053107B2

Reaction notes

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