2-Amino-2-methyl-1-propanol → HCID 90011361, compound

HRID 1481488Notes

Reaction equation

HRID 1481488 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([C:13]([F:16])([F:15])[F:14])=[CH:11][C:10]([C:17]([NH:19][C:20]([CH3:24])([CH3:23])[CH2:21]O)=[O:18])=[N:9]2)=[N:6][CH:7]=1.BrC1C=CC(N2C(C(F)(F)F)=CC(C(O)=O)=N2)=NC=1.C(Cl)(=O)C(Cl)=O.NC(C)(C)CO>C(Cl)Cl.O.CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([C:13]([F:16])([F:15])[F:14])=[CH:11][C:10]([C:17]3[O:18][CH2:23][C:20]([CH3:21])([CH3:24])[N:19]=3)=[N:9]2)=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 118072-Amino-2-methyl-1-propanolHCID 65578Oxalyl chlorideHCID 90011004HCID 90011004, compoundHCID 90011317HCID 90011317, compound

Product 1

HCID 90011361HCID 90011361, compoundYield 99%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

Step-1: 1-(5-Bromopyridin-2-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5-(trifluoromethyl)-1H-pyrazole-3-carboxamide: To (0° C.) cooled solution of 1-(5-bromopyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-3-carboxylic acid (500 mg, 1.48 mmol), in DCM (20 mL) was added oxalyl chloride (391 μL, 4.46 mmol) followed by catalytic amount of DMF. The resulting mixture was stirred at room temperature for 3 h. The solvent and excess of oxalyl chloride was then removed under vacuum and the resulting residue was dissloved in DCM (10 mL). A solution of 2-amino-2-methylpropan-1-ol (0.35 mL, 3.72 mmol) in DCM (5 mL) was then added to the above solution drop-wise at 0° C. and the resulting mixture was warmed to room temperature and then continued stirring at the same temperature for 18 h. Water (10 mL) was added to the above reaction followed by DCM (20 mL). The layers were separated and the aqueous layer was extracted with DCM (3×10 mL). The combined organic layers were washed with bine (10 mL), dried (anhydrous Na2SO4) and filtered. The filtrate was rotary evaporated and the crude product was purified by flash column chromatography to afford 600 mg (99%) of the title compound as white solid. 1HNMR (400 MHz, CDCl3) δ 8.61 (d, J=2.0 Hz, 1H), 8.04 (dd, J=2.0 & 8.0 Hz, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.37 (s, 1H), 6.96 (s, 1H, D2O exchangeable), 3.73 (s, 2H), 1.44 (s, 6H) ; ESI-MS (m/z) 407, 409 [(MH)+, Br79,81].

Workup

  1. customThe solvent and excess of oxalyl chloride was then removed under vacuum
  2. temperaturethe resulting mixture was warmed to room temperature
  3. stirringcontinued stirring at the same temperature for 18 h
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with DCM (3×10 mL)
  6. washThe combined organic layers were washed with bine (10 mL)
  7. dry with materialdried (anhydrous Na2SO4)
  8. filtrationfiltered
  9. customThe filtrate was rotary evaporated
  10. customthe crude product was purified by flash column chromatography

Sources & evidence

ORD record
ord-185e3726b58f4849bcb0611023ffcaeb
Source dataset
uspto-grants-2016_08
Patent number
US09409898B2

Reaction notes

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