Triethylamine → 3-(2,5-Dimethyl-pyrrol-1-yl)-5,6-bis-trifluoromethyl-pyridine-2-carboxylic acid (3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)-amide

HRID 444909Notes

Reaction equation

HRID 444909 reaction equation
[CH3:1][C:2]1[N:3]([C:8]2[C:9]([C:22]([OH:24])=O)=[N:10][C:11]([C:18]([F:21])([F:20])[F:19])=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.Cl.[NH2:26][CH2:27][C:28]([CH3:34])([OH:33])[C:29]([F:32])([F:31])[F:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>CN1C(=O)CCC1>[F:30][C:29]([F:32])([F:31])[C:28]([OH:33])([CH3:34])[CH2:27][NH:26][C:22]([C:9]1[C:8]([N:3]2[C:2]([CH3:1])=[CH:6][CH:5]=[C:4]2[CH3:7])=[CH:13][C:12]([C:14]([F:15])([F:17])[F:16])=[C:11]([C:18]([F:21])([F:19])[F:20])[N:10]=1)=[O:24]

Participants

6

Reactant 4

HCID 8471Triethylamine3×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 584423653-(2,5-Dimethyl-pyrrol-1-yl)-5,6-bis-trifluoromethyl-pyridine-2-carboxylic acid2×HCID 717573513-Amino-1,1,1-trifluoro-2-methylpropan-2-ol hydrochloride

Product 1

HCID 866576663-(2,5-Dimethyl-pyrrol-1-yl)-5,6-bis-trifluoromethyl-pyridine-2-carboxylic acid (3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)-amide

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a stirred solution of 3-(2,5-dimethyl-pyrrol-1-yl)-5,6-bis-trifluoromethyl-pyridine-2-carboxylic acid (Intermediate M) (1.16 g, 3.29 mmol) in NMP (32 ml) was added 3-Amino-1,1,1-trifluoro-2-methyl-propan-2-ol hydrochloride (commercially available) (591 mg, 3.29 mmol) followed by HATU (1.25 g, 3.29 mmol) and NEt3 (918 ul, 6.59 mmol) and the reaction mixture was left to stir at RT. After 1 h a further 0.2 equiv. NEt3 was added. After 15 min a further 0.4 equiv. NEt3 and 0.2 equiv. amine were added. After 30 min a further 0.1 equiv HATU was added. After 30 min most of the starting material had been consumed. The reaction mixture was added to EtOAc (50 ml), washed with 0.1M NaOH and the aqueous layer was back extracted with EtOAc (2×50 ml). The combined organic extracts were washed with water (2×150 ml), brine (100 ml), dried (MgSO4) and concentrated in vacuo to give the crude product as an orange oil.

Workup

  1. waitthe reaction mixture was left
  2. waitAfter 15 min a further 0.4 equiv
  3. customAfter 30 min most of the starting material had been consumed
  4. additionThe reaction mixture was added to EtOAc (50 ml)
  5. washwashed with 0.1M NaOH
  6. extractionthe aqueous layer was back extracted with EtOAc (2×50 ml)
  7. washThe combined organic extracts were washed with water (2×150 ml), brine (100 ml)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-77e5af32a767451a8b3d50c940b83391
Source dataset
uspto-grants-2013_07
Patent number
US08476269B2

Reaction notes

Loading…