Einecs 211-027-4 → HCID 178519562, compound

HRID 2177606Notes

Reaction equation

HRID 2177606 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]([N:14]1[CH2:19][CH2:18][C:17]2=[C:20]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[N:21](C)[N:22]=[C:16]2[CH2:15]1)=[O:13].[Cl-].[NH+]1C=CC=CC=1>>[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:9])[F:10])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]([N:14]1[CH2:19][CH2:18][C:17]2=[C:20]([C:24]3[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=3)[NH:21][N:22]=[C:16]2[CH2:15]1)=[O:13]

Participants

3

Reactant 2

HCID 69401Einecs 211-027-4HCID 90409201HCID 90409201, compound

Product 1

HCID 178519562HCID 178519562, compoundYield 19.3%

Conditions

Temperature
170 °C

Procedure

To a vial containing 6-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-(4-fluorophenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-c]pyridine (50 mg, 0.11 mmol) was added pyridinium chloride (270 mg, 2.30 mmol). The vial was flushed with N2 and heated to 170° C. for 30 min in a microwave reactor. To the reaction was added EtOAc and 1M NaOH. The layers were separated and the water layer was extracted with EtOAc three times. The combined organic layers were concentrated in vacuo and the residue was purified by HPLC (Gilson prep system, inertsil ODS-3, C18, 3 μm 30×100 mm column at 45° C., gradient of 5-70% MeCN/water with 0.05% TFA over 7 min, flow rate of 80 mL/min). The product was isolated as orange oil (9 mg, 19%) MS (ESI): mass calcd. for C20H14ClF4N3O, 423.8. m/z found, 424.2 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 7.82-7.69 (m, 1H), 7.58-7.38 (m, 4H), 7.18-7.13 (m, 2H), 5.01 (m, 1H), 4.48-4.39 (m, 1H), 4.30-3.87 (m, 1H), 3.60-3.40 (m, 1H), 2.94 (t, J=5.8 Hz, 1H), 2.86-2.65 (m, 1H).

Workup

  1. customThe vial was flushed with N2
  2. additionTo the reaction was added EtOAc and 1M NaOH
  3. customThe layers were separated
  4. extractionthe water layer was extracted with EtOAc three times
  5. concentrationThe combined organic layers were concentrated in vacuo
  6. customthe residue was purified by HPLC (Gilson prep system, inertsil ODS-3, C18, 3 μm 30×100 mm column at 45° C., gradient of 5-70% MeCN/water with 0.05% TFA over 7 min, flow rate of 80 mL/min)

Sources & evidence

ORD record
ord-8b90ce0c940e44638177dfe2c96dc3ea
Source dataset
uspto-grants-2015_06
Patent number
US09066946B2

Reaction notes

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