Diisopropylethylamine → 2-amino-N-(4-methoxypyridin-3-yl)-5-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 869122Notes

Reaction equation

HRID 869122 reaction equation
[NH2:1][C:2]1[C:14]([C:15]([OH:17])=O)=[C:5]2[N:6]=[C:7]([C:10]([F:13])([F:12])[F:11])[CH:8]=[CH:9][N:4]2[N:3]=1.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][N:23]=[CH:22][C:21]=1[NH2:26].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN1C(=O)CCC1>[NH2:1][C:2]1[C:14]([C:15]([NH:26][C:21]2[CH:22]=[N:23][CH:24]=[CH:25][C:20]=2[O:19][CH3:18])=[O:17])=[C:5]2[N:6]=[C:7]([C:10]([F:11])([F:12])[F:13])[CH:8]=[CH:9][N:4]2[N:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 52003433-Amino-4-methoxypyridineHCID 904168892-Amino-5-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

Product 1

HCID 782102422-amino-N-(4-methoxypyridin-3-yl)-5-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

2-Amino-5-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid 5a (100 mg, 0.4063 mmol), 4-methoxypyridin-3-amine (50.44 mg, 0.4063 mmol) and DIPEA (52.51 mg, 70.77 μL, 0.4063 mmol) were dissolved in dry NMP (812.6 μL) in a microwave tube. TBTU (130.5 mg, 0.4063 mmol) was added in one portion and the resulting mixture was stirred at RT for ˜10 minutes and at 100° C. for ˜2 h under microwave conditions. The reaction mixture was allowed to cool to RT and filtered through a SCX-2 cartridge (5 g). The cartridge was washed with MeOH/DCM and eluted with 2M NH3 in MeOH (3×10 mL). The eluate was concentrated under reduced pressure. The residue was purified by column chromatography on silica (7.5% MeOH in DCM, ˜75 mL) to give the desired Compound I-O-1 as a bright yellow solid (87.9 mg, 61% Yield). LC-MS (M+H)+353.1; 1H NMR (500 MHz, DMSO-d6) δ 9.93 (s, 1H), 9.55 (s, 1H), 9.26 (dd, 1H), 8.24 (dd, 1H), 7.50-7.51 (d, 1H), 7.17-7.18 (d, 1H), 6.99 (s, 2H), 4.00 (s, 3H).

Workup

  1. temperatureto cool to RT
  2. filtrationfiltered through a SCX-2 cartridge (5 g)
  3. washThe cartridge was washed with MeOH/DCM
  4. washeluted with 2M NH3 in MeOH (3×10 mL)
  5. concentrationThe eluate was concentrated under reduced pressure
  6. customThe residue was purified by column chromatography on silica (7.5% MeOH in DCM, ˜75 mL)

Sources & evidence

ORD record
ord-a8398a6e490b4fe7bcabda4844e3c825
Source dataset
uspto-grants-2015_03
Patent number
US08969360B2

Reaction notes

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