6-Amino-3-chloropyridazine → N-(6-chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide

HRID 538102Notes

Reaction equation

HRID 538102 reaction equation
[NH2:1][C:2]1[N:3]=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1.[F:9][C:10]([F:23])([F:22])[O:11][C:12]1[CH:13]=[C:14]([CH2:18][C:19](O)=[O:20])[CH:15]=[CH:16][CH:17]=1.CCN(C(C)C)C(C)C.CCCP(=O)=O.C(=O)(O)[O-].[Na+]>CN(C=O)C>[Cl:8][C:5]1[N:4]=[N:3][C:2]([NH:1][C:19](=[O:20])[CH2:18][C:14]2[CH:15]=[CH:16][CH:17]=[C:12]([O:11][C:10]([F:22])([F:9])[F:23])[CH:13]=2)=[CH:7][CH:6]=1

Participants

7

Reactant 5

HCID 216436-Amino-3-chloropyridazineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27773163-(Trifluoromethoxy)phenylacetic AcidHCID 16167369Propylphosphoric anhydride

Product 1

HCID 86687873N-(6-chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

3-Amino-6-chloropyridazine (55.5 g, 0.428 mol) and 3-(Trifluoromethoxy)phenylacetic acid (1.1 equiv., 0.471 mol, 104 g) were dissolved in DMF (30.0 vol., 1.66 L) in a 3000 mL three neck round-bottom flask. Addition of DIEA (1.1 equiv., 0.471 mol, 82 mL) via addition funnel was done over 5 minutes. Propylphosphonic anhydride solution (300 mL of a 50% solution in DMF, 1.1 equiv., 0.471 mol,) was charged into a 500 mL addition funnel and added dropwise to reaction solution (keeping reaction temperature≦+30° C.). The reaction usually goes to completion after 3 hours (TLC: 6:4 hexanes-ethyl acetate). Reaction mixture was then poured into 7.5% sodium bicarbonate (80.0 vol., 4.4 L) which was chilled in an ice bath. Off-white crystalline powder was filtered through a Büchner funnel, rinsed with water (20.0 vol., 1.1 L). Dried in a 50° C. vacuum to a constant weight to afford N-(6-chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide 1117: yield of 119.6 g (77%). 1H NMR (300 MHz, DMSO-d6) δ 11.63 (s, 1H), 8.38 (d, J=9.4 Hz, 1H), 7.88 (d, J=9.4 Hz, 1H), 7.52-7.27 (m, 4H), 3.90 (s, 2H).

Workup

  1. additionvia addition funnel
  2. additionadded dropwise to reaction solution (keeping reaction temperature≦+30° C.)
  3. customThe reaction
  4. waitusually goes to completion after 3 hours
  5. customReaction mixture
  6. temperaturewas chilled in an ice bath
  7. filtrationOff-white crystalline powder was filtered through a Büchner funnel
  8. washrinsed with water (20.0 vol., 1.1 L)
  9. customDried in a 50° C. vacuum to a constant weight

Sources & evidence

ORD record
ord-4d71f640a7214a85a954de09c21c8434
Source dataset
uspto-grants-2014_10
Patent number
US08865718B2

Reaction notes

Loading…