Diisopropylethylamine → N-Piperidin-4-yl-4-[8-(3-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-alpha]pyridin-2-ylamino]benzamide

HRID 57766Notes

Reaction equation

HRID 57766 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([C:9]2[C:10]3[N:11]([N:15]=[C:16]([NH:18][C:19]4[CH:27]=[CH:26][C:22]([C:23]([OH:25])=O)=[CH:21][CH:20]=4)[N:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH:6]=[CH:7][CH:8]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[NH2:63][CH:64]1[CH2:69][CH2:68][N:67](C(OC(C)(C)C)=O)[CH2:66][CH2:65]1>O1CCCC1.ClCCl>[NH:67]1[CH2:68][CH2:69][CH:64]([NH:63][C:23](=[O:25])[C:22]2[CH:21]=[CH:20][C:19]([NH:18][C:16]3[N:17]=[C:10]4[C:9]([C:5]5[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:29])[F:28])[CH:4]=5)=[CH:14][CH:13]=[CH:12][N:11]4[N:15]=3)=[CH:27][CH:26]=2)[CH2:65][CH2:66]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 445543244-(8-(3-(Trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)benzoic acid

Product 1

HCID 44554316N-Piperidin-4-yl-4-[8-(3-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-alpha]pyridin-2-ylamino]benzamideYield 42.3%

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

To a solution of 4-(8-(3-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)benzoic acid (1.0 g, 2.5 mmol, 1 equiv), O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.14 g, 3.00 mmol, 1.2 equiv), N,N-diisopropylethylamine (484 mg, 3.74 mmol, 1.5 equiv) in 2:1 tetrahydrofuran/dichloromethane (50 mL) was added tert-butyl 4-amino-1-piperidinecarboxylate (0.60 g, 3.0 mmol, 1.2 equiv) at room temperature. After 16 h, the reaction mixture was filtered, and the filtrate was concentrate. The resulting residue was dissolved in 1:1 trifluoroacetic acid/tetrahydrofuran (50 mL) at room temperature. After 2 h, the reaction mixture was concentrated in vacuo. Purification by preparative HPLC provided product (508 mg, 42%). LCMS (ESI) m/z: 481.0; 1H NMR (400 MHz, DMSO-d6) δ: 10.06 (s, 1H), 8.85 (d, J=7.6 Hz, 1H), 8.60 (s, 1H), 8.38 (d, J=8.8 Hz, 1H), 7.98 (d, J=8.8 Hz, 1H), 7.84 (br s, 2H), 7.72-7.79 (m, 3H), 7.32 (d, J=7.6 Hz, 2H), 7.15 (m, 1H), 4.02 (m, 1H), 3.27-3.32 (m, 2H), 2.95-3.05 (m, 2H), 1.87-1.94 (m, 2H), 1.41-1.48 (m, 2H).

Workup

  1. filtrationthe reaction mixture was filtered
  2. concentrationthe filtrate was concentrate
  3. dissolutionThe resulting residue was dissolved in 1:1 trifluoroacetic acid/tetrahydrofuran (50 mL) at room temperature
  4. waitAfter 2 h
  5. concentrationthe reaction mixture was concentrated in vacuo
  6. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-88c0d6d5f674426ba33482cf1126b6e4
Source dataset
uspto-grants-2016_09
Patent number
US09434732B2

Reaction notes

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