(2-Hydroxyphenyl)acetic acid → N-[3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-2-yl]-2-(2-hydroxyphenyl)acetamide

HRID 1912906Notes

Reaction equation

HRID 1912906 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([NH2:17])=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[N:13][C:12]=23)=[CH:4][CH:3]=1.[OH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[CH2:25][C:26](O)=[O:27].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>N1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([NH:17][C:26](=[O:27])[CH2:25][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[OH:18])=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[N:13][C:12]=23)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 11970(2-Hydroxyphenyl)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 687512953-(4-Chlorophenyl)pyrazolo[1,5-a]pyrimidin-2-amine

Product 1

HCID 68751195N-[3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-2-yl]-2-(2-hydroxyphenyl)acetamideYield 19.3%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
35 °C

Procedure

The product from Example 99A (100 mg, 0.41 mmol), 2-hydroxyphenylacetic acid (124 mg, 0.82 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (157 mg, 0.82 mmol), 1-hydroxybenzotriazole hydrate (100 mg, 0.65 mmol) were combined with pyridine (8 mL) and stirred at 35° C. for 18 hours. 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, 5-95% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford 30 mg (19%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.28-10.56 (bs, 1H), 9.09 (dd, J=6.9, 1.7 Hz, 1H), 8.62 (dd, J=4.1, 1.7 Hz, 1H), 7.70-7.73 (m, 2H), 7.30-7.34 (m, 2H), 7.11-7.16 (m, 2H), 6.72-6.81 (m, 2H), 6.65-6.72 (m, 1H), 3.57 (s, 2H); MS (ESI) m/z 379 (M+H)+; Anal. calculated for C20H15ClN4O2.0.35H2O: C, 62.37; H, 4.11; N, 14.55. Found C, 62.16; H, 3.87; N, 14.49.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. custompurified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 5-95% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

Sources & evidence

ORD record
ord-dac0b7bb391843e7b2733810a4777214
Source dataset
uspto-grants-2013_12
Patent number
US08609669B2

Reaction notes

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