Diisopropylethylamine → HCID 69631191, compound

HRID 1407999Notes

Reaction equation

HRID 1407999 reaction equation
[F:1][C:2]([F:44])([F:43])[C:3]1[CH:4]=[C:5]([CH:40]=[CH:41][CH:42]=1)[CH2:6][NH:7][C:8]([C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]2[CH:21]=[C:20]([N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)[CH:19]=[CH:18][C:17]=2[NH:28][C:29]([C:31]2[CH:32]=[C:33]([CH:37]=[CH:38][CH:39]=2)[C:34](O)=[O:35])=[O:30])[CH:11]=1)=[O:9].C(N(C(C)C)CC)(C)C.[NH:54]1[CH2:59][CH2:58][CH:57]([CH2:60][C:61]([O:63]CC)=[O:62])[CH2:56][CH2:55]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[N:22]1([C:20]2[CH:19]=[CH:18][C:17]([NH:28][C:29]([C:31]3[CH:32]=[C:33]([CH:37]=[CH:38][CH:39]=3)[C:34]([N:54]3[CH2:55][CH2:56][CH:57]([CH2:60][C:61]([OH:63])=[O:62])[CH2:58][CH2:59]3)=[O:35])=[O:30])=[C:16]([C:12]3[CH:11]=[C:10]([C:8](=[O:9])[NH:7][CH2:6][C:5]4[CH:40]=[CH:41][CH:42]=[C:3]([C:2]([F:1])([F:43])[F:44])[CH:4]=4)[CH:15]=[CH:14][N:13]=3)[CH:21]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2760465Ethyl 2-(piperidin-4-yl)acetateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 665867843-((2-(4-((3-(Trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)phenyl)carbamoyl)benzoic acid

Product 1

HCID 69631191HCID 69631191, compoundYield 45.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 20 mg of 3-((4-(piperidin-1-yl)-2-(4-((3-(trifluoromethyl)-benzyl)carbamoyl)pyridin-2-yl)phenyl)carbamoyl)benzoic acid 4.1e, 28 mg of diisopropylethylamine, and 6.5 mg of ethyl 2-(piperidin-4-yl)acetate in 1 mL of DMF was added 17 mg of HATU. The mixture was stirred at 60° C. for 1 h. The solution was diluted with water and extracted with ethyl acetate. The organic phase was washed with water, then brine. It was dried and the solvent was evaporated at reduced pressure. It was dissolved in 4:1 methanol/water and treated with 19.4 mg of LiOH.H2O. After stirring for 20 h the product was isolated by reverse phase HPLC, eluting with 0.5% TFA in a gradient of water and acetonitrile to give 10.9 mg of product. MS (ES, m/z): 728.7 [M+H]+.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic phase was washed with water
  3. customIt was dried
  4. customthe solvent was evaporated at reduced pressure
  5. dissolutionIt was dissolved in 4:1 methanol/water
  6. additiontreated with 19.4 mg of LiOH.H2O
  7. stirringAfter stirring for 20 h the product
  8. customwas isolated by reverse phase HPLC
  9. washeluting with 0.5% TFA in a gradient of water and acetonitrile

Sources & evidence

ORD record
ord-139880a4f9a64c6196d60f120a7ddf71
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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