Triethylamine → N-(6-(1-(2-cyanamido-2-oxoethyl)-6-oxo-1,6-dihydropyridin-3-yl)-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

HRID 869978Notes

Reaction equation

HRID 869978 reaction equation
[F:1][C:2]1([F:35])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[CH:24]=[CH:25][C:26](=[O:33])[N:27]([CH2:29][C:30]([OH:32])=O)[CH:28]=5)[C:20]([CH3:34])=[CH:19][CH:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.[N:36]#[C:37][NH2:38].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[NH:38]([C:30](=[O:32])[CH2:29][N:27]1[C:26](=[O:33])[CH:25]=[CH:24][C:23]([C:21]2[N:22]=[C:17]([NH:16][C:14]([C:11]3([C:9]4[CH:8]=[CH:7][C:5]5[O:6][C:2]([F:35])([F:1])[O:3][C:4]=5[CH:10]=4)[CH2:13][CH2:12]3)=[O:15])[CH:18]=[CH:19][C:20]=2[CH3:34])=[CH:28]1)[C:37]#[N:36]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9864CyanamideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 687967092-(5-(6-(1-(2,2-difluorobenzo[d][1,3]-dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)-2-oxopyridin-1(2H)-yl)acetic acid

Product 1

HCID 89228846N-(6-(1-(2-cyanamido-2-oxoethyl)-6-oxo-1,6-dihydropyridin-3-yl)-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamideYield 32.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 2-(5-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)-2-oxopyridin-1(2H)-yl)acetic acid (0.13 g, 0.27 mmol), cyanamide (27 μL, 0.32 mmol), and triethylamine (75 μL, 0.54 mmol) in N,N-dimethylformamide (3 mL) was added 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.12 g, 0.33 mmol) and the reaction mixture was stirred at room temperature for 1 hour. At this point the reaction mixture was filtered and purified by reverse-phase HPLC. The resulting trifluoroacetic acid salt was dissolved in dichloromethane and washed with a saturated sodium bicarbonate solution and 1N Hydrochloric acid. The organics were dried over sodium sulfate and evaporated to dryness to give the product (45 mg, 31%). ESI-MS m/z calc. 507.14. found 508.4 (M+1)+ Retention time 1.63 minutes.

Workup

  1. filtrationAt this point the reaction mixture was filtered
  2. custompurified by reverse-phase HPLC
  3. dissolutionThe resulting trifluoroacetic acid salt was dissolved in dichloromethane
  4. washwashed with a saturated sodium bicarbonate solution and 1N Hydrochloric acid
  5. dry with materialThe organics were dried over sodium sulfate
  6. customevaporated to dryness

Sources & evidence

ORD record
ord-78f7ff7e3d0e4e4885bb1eb8bbd2fb11
Source dataset
uspto-grants-2015_03
Patent number
US08969386B2

Reaction notes

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