3-Methyl-3-phenylbutanoyl chloride → N-[3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-2-yl]-3-methyl-3-phenylbutanamide

HRID 1912922Notes

Reaction equation

HRID 1912922 reaction equation
[CH3:1][C:2]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH3:7])[CH2:3][C:4](Cl)=[O:5].[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:22]([NH2:30])=[N:23][N:24]3[CH:29]=[CH:28][CH:27]=[N:26][C:25]=23)=[CH:17][CH:16]=1>N1C=CC=CC=1>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:22]([NH:30][C:4](=[O:5])[CH2:3][C:2]([CH3:7])([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH3:1])=[N:23][N:24]3[CH:29]=[CH:28][CH:27]=[N:26][C:25]=23)=[CH:17][CH:16]=1

Participants

4

Reactant 2

HCID 128675683-Methyl-3-phenylbutanoyl chlorideHCID 687512953-(4-Chlorophenyl)pyrazolo[1,5-a]pyrimidin-2-amine

Product 1

HCID 68751279N-[3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-2-yl]-3-methyl-3-phenylbutanamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To the product from Example 117A (82 mg, 0.42 mmol) was added a solution of the product from Example 99A (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 the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.13-10.16 (bs, 1H), 9.09 (dd, J=7.0, 1.7 Hz, 1H), 8.60 (dd, J=4.1, 1.7 Hz, 1H), 7.68-7.72 (m, 2H), 7.40-7.45 (m, 4H), 7.27-7.35 (m, 2H), 7.15-7.22 (m, 1H), 7.12 (dd, J=7.0, 4.1 Hz, 1H), 2.70 (s, 2H), 1.41 (s, 6H); MS (ESI) m/z 405 (M+H)+; Anal. calculated for C23H21ClN4O.0.1H2O: C, 67.93; H, 5.25; N, 13.78. Found C, 67.65; H, 5.08; N, 13.61.

Workup

  1. waitat 40° C. for 1 hour
  2. concentrationThe reaction mixture was concentrated under vacuum
  3. 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-8c92a424191245a08f9d74f3a1a2aa79
Source dataset
uspto-grants-2013_12
Patent number
US08609669B2

Reaction notes

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