4-(Trifluoromethoxy)benzoyl Chloride → HCID 59327622, compound

HRID 1257072Notes

Reaction equation

HRID 1257072 reaction equation
[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:12]=[CH:11][C:7]([C:8](Cl)=[O:9])=[CH:6][CH:5]=1.[NH2:15][C@:16]([CH3:30])([CH2:19][N:20]1[CH:29]=[C:23]2[N:24]=[CH:25][C:26]([Br:28])=[CH:27][C:22]2=[N:21]1)[C:17]#[N:18]>C1COCC1>[Br:28][C:26]1[CH:25]=[N:24][C:23]2=[CH:29][N:20]([CH2:19][C@@:16]([NH:15][C:8](=[O:9])[C:7]3[CH:11]=[CH:12][C:4]([O:3][C:2]([F:14])([F:13])[F:1])=[CH:5][CH:6]=3)([C:17]#[N:18])[CH3:30])[N:21]=[C:22]2[CH:27]=1

Participants

4

Reactant 2

HCID 1421104-(Trifluoromethoxy)benzoyl ChlorideHCID 67381248HCID 67381248, compound

Product 1

HCID 59327622HCID 59327622, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

4-Trifluoromethoxybenzoyl chloride (14.5 mL) was added at around 0° C. to a cold solution of (R)-2-amino-3-(6-bromo-pyrazolo[4,3-b]pyridin-2-yl)-2-methyl-propionitrile (23.4 g, 95% ee) in dry THF (600 mL) mixed with TEA (13.4 mL). The reaction mixture was stirred for around 4 hours at around 0° C. The cold reaction mixture was then filtered through a short plug of Celite® and basic alumina and solvent evaporated under reduced pressure. The resulting residue was triturated with DCM to afford a solid that was isolated by filtration to give the title compound as a white solid (28.6 g, 73.1%, 99.6% analytical purity, 99% ee). The filtrate was collected and solvent evaporated under reduced pressure. The residue was loaded on silica gel and purified by chromatography (SiO2, heptane/EA) to afford a second crop of title compound as a white solid (4.1 g, 10.5%). MS (ES): M/Z [M+H]=468. 1H NMR: (400 MHz, CHLOROFORM-d): 1.94 (s, 3H), 4.86 (d, J=14.0 Hz, 1H), 5.02 (d, J=14.0 Hz, 1H), 7.33 (d, J=8.1 Hz, 2H), 7.83-7.92 (m, 2H), 8.02 (s, 1H), 8.21 (dd, J=2.0, 0.7 Hz, 1H), 8.40 (d, J=0.7 Hz, 1H) and 8.62 (d, J=2.0 Hz, 1H). 19F NMR (376 MHz, CHLOROFORM-d): −58.1 (s, 3F).

Workup

  1. customThe cold reaction mixture
  2. filtrationwas then filtered through a short plug of Celite® and basic alumina and solvent
  3. customevaporated under reduced pressure
  4. customThe resulting residue was triturated with DCM
  5. customto afford a solid
  6. customthat was isolated by filtration

Sources & evidence

ORD record
ord-b1b5ea5607e9404c89046181e0e89b33
Source dataset
uspto-grants-2013_06
Patent number
US08461176B2

Reaction notes

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