Diisopropylethylamine → N-(2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl)-1-(dimethylamino)-N-methylcyclopropane-carboxamide

HRID 912542Notes

Reaction equation

HRID 912542 reaction equation
[CH3:1][N:2]1[C:10]2[CH:9]=[C:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][NH:20][CH3:21])=[C:13]([C:22]([F:25])([F:24])[F:23])[CH:12]=3)[N:7]=[C:6]([C:26]#[N:27])[C:5]=2[N:4]=[CH:3]1.[CH3:28][N:29]([CH3:36])[C:30]1([C:33](O)=[O:34])[CH2:32][CH2:31]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN1C(=O)CCC1.CCOC(C)=O.CCOCC>[C:26]([C:6]1[C:5]2[N:4]=[CH:3][N:2]([CH3:1])[C:10]=2[CH:9]=[C:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][N:20]([CH3:21])[C:33]([C:30]3([N:29]([CH3:36])[CH3:28])[CH2:32][CH2:31]3)=[O:34])=[C:13]([C:22]([F:25])([F:23])[F:24])[CH:12]=2)[N:7]=1)#[N:27]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 3861991-(Dimethylamino)cyclopropanecarboxylicacidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594106391-methyl-6-(4-(2-(methylamino)ethoxy)-3-(trifluoromethyl)-phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile

Product 1

HCID 59410641N-(2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl)-1-(dimethylamino)-N-methylcyclopropane-carboxamideYield 22%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

1-Methyl-6-(4-(2-(methylamino)ethoxy)-3-(trifluoromethyl)phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile (54 mg), 1-(dimethylamino)cyclopropane-carboxylic acid (37.2 mg), HATU (82 mg) and DIPEA (0.119 ml) were combined in NMP (2 ml) and stirred at room temperature for 16 hours. The reaction mixture was diluted with EtOAc (25 mL) and washed with 1:1 saturated sodium bicarbonate solution/water (3×15 mL). Organics were dried over sodium sulphate and solvent evaporated under reduced pressure. Purification by flash chromatography (10 g silica column, DCM to 5% MeOH in DCM gradient) followed by preparative HPLC (acidic) and SCX afforded N-(2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl)-1-(dimethylamino)-N-methylcyclopropane-carboxamide (22% yield) as a white solid after trituration with ether and oven drying.

Workup

  1. washwashed with 1:1 saturated sodium bicarbonate solution/water (3×15 mL)
  2. dry with materialOrganics were dried over sodium sulphate and solvent
  3. customevaporated under reduced pressure
  4. customPurification by flash chromatography (10 g silica column, DCM to 5% MeOH in DCM gradient)

Sources & evidence

ORD record
ord-472a3a2fd6d0491291a28075a3cb5f03
Source dataset
uspto-grants-2011_09
Patent number
US08026236B2

Reaction notes

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