Cyclopropylamine → HCID 66666472, compound

HRID 1618027Notes

Reaction equation

HRID 1618027 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]([C:20]1[CH:28]=[CH:27][C:23]([C:24](O)=[O:25])=[CH:22][CH:21]=1)[CH2:10][C:11]([C:13]1[CH:18]=[CH:17][N:16]=[C:15]([CH3:19])[CH:14]=1)=[O:12].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2[N:41]=[CH:42][CH:43]=[CH:44]C=2N=N1.C1(N)CC1.C(=O)([O-])O.[Na+]>ClCCl.C(N(CC)CC)C>[CH:42]1([NH:41][C:24](=[O:25])[C:23]2[CH:22]=[CH:21][C:20]([CH:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])[CH2:10][C:11]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]([CH3:19])[CH:14]=3)=[O:12])=[CH:28][CH:27]=2)[CH2:44][CH2:43]1

Participants

7

Reactant 4

HCID 69828CyclopropylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66666664HCID 66666664, compound

Product 1

HCID 66666472HCID 66666472, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 4-[1-(2,4-difluoro-phenyl)-3-(2-methyl-pyridin-4-yl)-3-oxo-propyl]-benzoic acid (40 mg) in dichloromethane (1.5 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (48 mg) and triethylamine (29 μL) and the reaction mixture stirred at 40° C. After 15 min, cyclopropylamine (157 μL; CAS RN 765-30-0) was added and stirring continued for 2 h at 40° C. A saturated aq. solution of sodium hydrogencarbonate (50 mL) was added, the phases separated and the aqueous layer extracted with ethyl acetate (3×100 mL). The combined organic phases were dried over sodium sulfate and the crude reaction product purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane/ethyl acetate (100:0 to 50:50) to give the title compound as a light yellow solid. MS (ESI+): m/z=421.1 ([M+H]+).

Workup

  1. stirringstirring
  2. waitcontinued for 2 h at 40° C
  3. customthe phases separated
  4. extractionthe aqueous layer extracted with ethyl acetate (3×100 mL)
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. customthe crude reaction product
  7. custompurified by silica gel chromatography
  8. washeluting with a gradient of n-heptane/ethyl acetate (100:0 to 50:50)

Sources & evidence

ORD record
ord-26433c355be441bcaa1f32cf3c86ad01
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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