Sodium Bicarbonate → HCID 42602132, compound

HRID 1014099Notes

Reaction equation

HRID 1014099 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[N:22]=[CH:21][N:20]=[C:19]([NH:23]NC3C=CC=CC=3)[CH:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.Cl.[CH3:32][N:33]([CH3:40])[CH2:34]/[CH:35]=[CH:36]/[C:37](Cl)=[O:38].C(=O)(O)[O-].[Na+]>CN1CCCC1=O.C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[N:22]=[CH:21][N:20]=[C:19]([NH:23][C:2]3[CH:3]=[C:4]([NH:16][C:37](=[O:38])/[CH:36]=[CH:35]/[CH2:34][N:33]([CH3:40])[CH3:32])[CH:5]=[CH:6][CH:7]=3)[CH:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 21917321(E)-4-(diMethylaMino)but-2-enoyl chlorideHCID 86630627HCID 86630627, compound

Product 1

HCID 42602132HCID 42602132, compoundYield 6.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

3-{[6-(3-chloro-4-(2-pyridyl)methoxyphenylamino)-pyrimidin-4-ylamino]phenylamine (IR-9) was dissolved in N-methylpyrrolidinone (1.2 mL) and added dropwise over 10 minutes to the ice-cold solution of (E)-4-(dimethylamino)but-2-enoyl chloride hydrochloride in acetonitrile. The reaction was stirred in an ice bath for 2 hr. To the mixture was added sodium bicarbonate to pH greater than 9. The oil that formed was extracted with EtOAc (3×25 mL). A portion of the material was insoluble and set aside. The organic layer was dried (MgSO4) filtered and evaporated to a dark red oil. Both oils contained substantial amount of product as shown by TLC:SiO2 CHCl3:MeOH/NH4OH (8:1) 19:1. The oils were combined and purified by flash column chromatography silica gel (25×300 mm) eluted first with 5% methanol/ammonium hydroxide 8/1 to remove non-polar impurities followed by 10% methanol/ammonium hydroxide 8/1 to elute 59 mg of product. The sample was further purified by a second flash column chromatography silica gel (25×250 mm) eluted with 10% methanol/ammonium hydroxide 8/1 to give the title compound (16.3 mg, 0.03 mmol, 6.4% yield). MS (ES+) 530 (M+): 552, (M+Na); 1H NMR (DMSO-d6, 500 MHz) δ (ppm): 10.04 (s, 1H), 9.19 (s, 1H), 9.14 (s, 1H), 8.60 (s, 1H), 8.27 (s, 1H), 7.88 (s, 2H), 7.57 (s, 1H), 7.36 (d, 1H, J=7.4 Hz), 7.29 (d, 2H, J=7.8 Hz), 7.22 (d, 2H, J=7.9 Hz), 7.18 (m, 2H), 6.74 (m, 1H), 6.30 (d, 1H, J=15 Hz) 6.10 (s, 1H), 5.24 (s, 2H), 3.06 (s, 2H), 2.18 (s, 6H) ppm; HPLC: tR=5.15 min, 97.5% (YMC-Pack ODS-A 4.6×100 mm, 80% water/20% acetonitrile to 5% water/95% acetonitrile over 5.5 min, hold to 9 min.).

Workup

  1. customThe oil that formed
  2. extractionwas extracted with EtOAc (3×25 mL)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated to a dark red oil
  6. custompurified by flash column chromatography silica gel (25×300 mm)
  7. washeluted first with 5% methanol/ammonium hydroxide 8/1
  8. customto remove non-polar impurities
  9. washto elute 59 mg of product
  10. customThe sample was further purified by a second flash column chromatography silica gel (25×250 mm)
  11. washeluted with 10% methanol/ammonium hydroxide 8/1

Sources & evidence

ORD record
ord-87eb4459c37245349711393a6f0977bc
Source dataset
uspto-grants-2011_07
Patent number
US07982036B2

Reaction notes

Loading…