Triethylamine → N-[4-(3-Dimethylamino-prop-1-ynyl)-3-trifluoromethyl-phenyl]-2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-acetamide

HRID 1660975Notes

Reaction equation

HRID 1660975 reaction equation
CCCP(=O)=O.[N:7]1[C:15]2[C:10](=[N:11][CH:12]=[CH:13][CH:14]=2)[N:9]([C:16]2[CH:21]=[CH:20][C:19]([CH2:22][C:23]([OH:25])=O)=[CH:18][CH:17]=2)[CH:8]=1.[CH3:26][N:27]([CH3:42])[CH2:28][C:29]#[C:30][C:31]1[CH:36]=[CH:35][C:34]([NH2:37])=[CH:33][C:32]=1[C:38]([F:41])([F:40])[F:39].CCN(CC)CC>CN(C1C=CN=CC=1)C.CN(C=O)C.CCOC(C)=O>[CH3:42][N:27]([CH3:26])[CH2:28][C:29]#[C:30][C:31]1[CH:36]=[CH:35][C:34]([NH:37][C:23](=[O:25])[CH2:22][C:19]2[CH:18]=[CH:17][C:16]([N:9]3[C:10]4=[N:11][CH:12]=[CH:13][CH:14]=[C:15]4[N:7]=[CH:8]3)=[CH:21][CH:20]=2)=[CH:33][C:32]=1[C:38]([F:39])([F:40])[F:41]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 16167369Propylphosphoric anhydrideHCID 53213084(4-Imidazo[4,5-b]pyridin-3-yl-phenyl)-acetic acidHCID 670216344-(3-Dimethylamino-prop-1-ynyl)-3-trifluoromethyl-phenylamine

Product 1

HCID 11993289N-[4-(3-Dimethylamino-prop-1-ynyl)-3-trifluoromethyl-phenyl]-2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-acetamide

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Propylphosphonic anhydride (50% in DMF, 0.69 mL, 1.19 mmol, 2 equiv) is added to a solution of (4-imidazo[4,5-b]pyridin-3-yl-phenyl)acetic acid (Step 7.1) (0.150 g, 0.59 mmol), 4-(3-dimethylamino-prop-1-ynyl)-3-trifluoromethyl-phenylamine (0.138 g, 0.57 mmol, 0.95 equiv), DMAP (10 mg), and Et3N (0.82 mL, 5.93 mmol, 10 equiv) in DMF (2.0 mL), at rt and under an argon atmosphere. The reaction mixture is stirred at rt for 18 h, diluted with EtOAc and washed with H2O. The aqueous layer is extracted with EtOAc. The combined organic phase is washed with brine, dried (Na2SO4), filtered and concentrated. The residue is purified by reversed phase MPLC (CH3CN/H2O/TFA) to provide the title compound as a white solid: ES-MS: 477.9 [M+H]+; single peak at tR=3.20 min (System 1); Rf=0.06 (CH2Cl2/NH3 (2 N in MeOH), 95:5).

Workup

  1. washwashed with H2O
  2. extractionThe aqueous layer is extracted with EtOAc
  3. washThe combined organic phase is washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by reversed phase MPLC (CH3CN/H2O/TFA)

Sources & evidence

ORD record
ord-f507071e7c6b4b928074fc53565ed08b
Source dataset
uspto-grants-2011_10
Patent number
US08030311B2

Reaction notes

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