Triethylamine → 1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-N-(2-(trifluoromethoxy)ethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide

HRID 1753246Notes

Reaction equation

HRID 1753246 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]([CH2:9][N:10]2[C:18]3[C:13](=[N:14][CH:15]=[CH:16][CH:17]=3)[C:12]([C:19]([OH:21])=O)=[CH:11]2)[C:4]=1[CH3:22].CN1C(=O)CCC1.C(N(CC)CC)C.Cl.[F:38][C:39]([F:45])([F:44])[O:40][CH2:41][CH2:42][NH2:43].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CO>[CH3:1][O:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]([CH2:9][N:10]2[C:18]3[C:13](=[N:14][CH:15]=[CH:16][CH:17]=3)[C:12]([C:19]([NH:43][CH2:42][CH2:41][O:40][C:39]([F:45])([F:44])[F:38])=[O:21])=[CH:11]2)[C:4]=1[CH3:22]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 13387N-methyl-2-pyrrolidoneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 448908072-(Trifluoromethoxy)ethan-1-amine hydrochlorideHCID 1178190601-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid

Product 1

HCID 904668551-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-N-(2-(trifluoromethoxy)ethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamideYield 28.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

See FIG. 21(c). 1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid (40 mg, 0.13 mmol) was taken in a 50 ml single necked flask equipped with an air condenser connected to nitrogen source. NMP (3 ml, 31.17 mmol) was added to get a solution. Triethyl amine (0.056 ml, 0.40 mmol) was added followed by the addition of 2-(trifluoromethoxy)ethanamine hydrochloride (44.4 mg, 0.27 mmol). The reaction mass was stirred at RT for 5 minutes. HATU (61.2 mg, 0.16 mmol) was added and stirred at RT for 30 min. After the completion of the reaction, few drops of methanol was added and clear solution was subjected for reverse phase HPLC purification to get 1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-N-(2-(trifluoromethoxy)ethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide (15.00 mg, 27.3%). ES+MS m/z: 410 (M+1). 1H NMR (300 MHz, DMSO-d6) δ ppm 2.25 (s, 3 H ) 3.68-3.80 (m, 2 H ) 3.93 (s, 3 H ) 4.24 (t, J=5.27 Hz, 2 H ) 5.69 (s, 2 H ) 7.26 (dd, J=8.29, 4.71 Hz, 1 H ) 7.94 (d, J=7.35 Hz, 1 H ) 8.28 (s, 1 H ) 8.38-8.54 (m, 2 H ) 8.96 (s, 1 H).

Workup

  1. customequipped with an air condenser
  2. customto get a solution
  3. stirringstirred at RT for 30 min
  4. additionwas added
  5. customclear solution was subjected for reverse phase HPLC purification

Sources & evidence

ORD record
ord-49294fb0aab042b3b2c12886c3413a1f
Source dataset
uspto-grants-2015_10
Patent number
US09163020B2

Reaction notes

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