Pyridine → Butanamide, 3,3-dimethyl-N-[3-[4-(trifluoromethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-2-yl]-

HRID 1912891Notes

Reaction equation

HRID 1912891 reaction equation
[F:1][C:2]([F:21])([F:20])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:11]([NH2:19])=[N:12][N:13]3[CH:18]=[CH:17][CH:16]=[N:15][C:14]=23)=[CH:6][CH:5]=1.N1C=CC=CC=1.[CH3:28][C:29]([CH3:35])([CH3:34])[CH2:30][C:31](Cl)=[O:32]>ClCCl>[CH3:28][C:29]([CH3:35])([CH3:34])[CH2:30][C:31]([NH:19][C:11]1[C:10]([C:7]2[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:20])[F:21])=[CH:9][CH:8]=2)=[C:14]2[N:15]=[CH:16][CH:17]=[CH:18][N:13]2[N:12]=1)=[O:32]

Participants

5

Reactant 3

HCID 1049PyridineHCID 815143,3-Dimethylbutanoyl chlorideHCID 687492143-[4-(Trifluoromethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-2-amine

Product 1

HCID 68751383Butanamide, 3,3-dimethyl-N-[3-[4-(trifluoromethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-2-yl]-Yield 89.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the product from Example 1C (0.318 g, 1.081 mmol) in dichloromethane (8 mL) was added pyridine (0.256 g, 3.24 mmol). 3,3-Dimethylbutanoyl chloride (0.160 g, 1.189 mmol) was slowly added and the resulting reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated and the residue was purified by preparative HPLC on a Phenomenex Luna C8(2) 5 um 100 Å AXIA column (30 mm×75 mm). A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 50 mL/min (0-0.5 min 10% A, 0.5-6.0 min linear gradient 10-100% A, 6.0-7.0 min 100% A, 7.0-8.0 min linear gradient 100-10% A) to yield the title compound (0.38 g, 88%). 1H NMR (400 MHz, CD3Cl) δ ppm 1.11 (s, 6H) 2.33 (s, 2H) 6.86 (dd, J=6.94, 4.12 Hz, 1H) 7.30-7.42 (m, 3H) 7.63-7.79 (m, 2H) 8.51 (dd, J=4.12, 1.73 Hz, 1H) 8.68 (dd, J=6.94, 1.63 Hz, 1H). MS ESI(+) m/z 393.4 [M+H]+.

Workup

  1. customthe resulting reaction mixture
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue was purified by preparative HPLC on a Phenomenex Luna C8(2) 5 um 100 Å AXIA column (30 mm×75 mm)
  4. customwas used, at a flow rate of 50 mL/min (0-0.5 min 10% A, 0.5-6.0 min linear gradient 10-100% A, 6.0-7.0 min 100% A, 7.0-8.0 min linear gradient 100-10% A)

Sources & evidence

ORD record
ord-ccd0f721a5f94875b77f190eb30a76cf
Source dataset
uspto-grants-2013_12
Patent number
US08609669B2

Reaction notes

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