Dimethylformamide → 2-(pyridin-3-yl)-N-{3-[4-(trifluoromethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-2-yl}acetamide

HRID 1912901Notes

Reaction equation

HRID 1912901 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][C:9]([OH:11])=O)[CH:3]=1.C(Cl)(=O)C(Cl)=O.CN(C)C=O.[F:23][C:24]([F:43])([F:42])[O:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[C:33]([NH2:41])=[N:34][N:35]3[CH:40]=[CH:39][CH:38]=[N:37][C:36]=23)=[CH:28][CH:27]=1>ClCCl.N1C=CC=CC=1>[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][C:9]([NH:41][C:33]2[C:32]([C:29]3[CH:28]=[CH:27][C:26]([O:25][C:24]([F:43])([F:23])[F:42])=[CH:31][CH:30]=3)=[C:36]3[N:37]=[CH:38][CH:39]=[CH:40][N:35]3[N:34]=2)=[O:11])[CH:3]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 27237243-Pyridineacetic acid, hydrochloride (1:1)HCID 687492143-[4-(Trifluoromethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-2-amine

Product 1

HCID 687546322-(pyridin-3-yl)-N-{3-[4-(trifluoromethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-2-yl}acetamideYield 29%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

3-Pyridylacetic acid hydrochloride (41.6 mg, 0.239 mmol) was suspended in dichloromethane (3.0 mL). Oxalyl chloride (24 μL, 0.28 mmol) and a drop of dimethylformamide were added and the mixture was stirred at ambient temperature for 90 minutes. The reaction mixture was concentrated under vacuum. To this residue was added a solution of the product from Example 1C (59 mg, 0.2 mmol) in pyridine (2.0 mL). The mixture was stirred at ambient temperature for 1 hour and then at 40° C. for 1 hour. The reaction mixture was concentrated under vacuum and purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 30-100% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford 24 mg (29%) of the title compound. 1H NMR (400 MHz, CD3OD) δ ppm 8.86 (d, J=5.8 Hz, 1H), 8.52-8.59 (m, 2H), 8.44-8.49 (m, 1H), 7.79-7.89 (m, 1H), 7.71-7.74 (m, 2H), 7.33-7.44 (m, 1H), 7.20-7.23 (m, 2H), 7.07 (dd, J=7.0, 4.1 Hz, 1H), 3.81 (s, 2H); MS (ESI) m/z 414 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. stirringThe mixture was stirred at ambient temperature for 1 hour
  3. waitat 40° C. for 1 hour
  4. concentrationThe reaction mixture was concentrated under vacuum
  5. custompurified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 30-100% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

Sources & evidence

ORD record
ord-5e2c668409524f84be12ed0948efbf1e
Source dataset
uspto-grants-2013_12
Patent number
US08609669B2

Reaction notes

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