Hydrochloric Acid → HCID 18782123, compound

HRID 1420556Notes

Reaction equation

HRID 1420556 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]([CH2:15][Cl:16])[CH2:7][N:8]2[S:11]([CH3:14])(=[O:13])=[O:12])=[CH:4][CH:3]=1.[N+:17]([C:20]1[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][CH:21]=1)([O-:19])=[O:18].O.C1(C)C(S(O)(=O)=O)=CC=CC=1.C([BH3-])#N.Cl>C1C=CC=CC=1>[Cl:16][CH2:15][CH:6]1[C:5]2[C:9](=[CH:10][C:2]([NH:1][CH2:24][C:23]3[CH:26]=[CH:27][C:20]([N+:17]([O-:19])=[O:18])=[CH:21][CH:22]=3)=[CH:3][CH:4]=2)[N:8]([S:11]([CH3:14])(=[O:12])=[O:13])[CH2:7]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 5414-NitrobenzaldehydeHCID 387492HCID 387492, compoundHCID 498716Cyano-borohydrideHCID 124969952-Methylbenzenesulfonic acid hydrate

Product 1

HCID 18782123HCID 18782123, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

A mixture of 6-amino-3-(chloromethyl)-1-(methanesulfonyl)indoline (29) [Tercel, M., Denny, W. A. and Wilson, W. R., Bioorg. Med. Chem. Lett., 1996, in press] (73 mg, 0.28 mmol), 4-nitrobenzaldehyde (51 mg, 0.34 mmol) and toluenesulfonic acid monohydrate (5 mg, 0.3 mmol) in benzene (30 mL) was heated to reflux and most of the benzene slowly distilled off over 40 min. The remaining orange-brown solution was cyanoborohydride (35 mg, 0.56 mmol) then 2N HCl (0.5 mL) were added and the mixture was stirred at 20 C for 40 min, then evaporated. The residue was diluted with water, extracted with EtOAc (×2), and the extracts dried (Na2SO4) and evaporated. Dry column chromatography, eluting with EtOAc/petroleum ether (1:2), gave 3-(chloromethyl)-1-(methanesulfonyl)-6-[(4-nitrobenzyl)amino]indoline (30) as a yellow oil (96 mg, 87%). 1H NMR (CDCl3) a 8.19 (d, J=8.8 Hz, 2 H, ArH o to NO2), 7.52 (d, J=8.8 Hz, 2 H, ArH m to NO2), 7.00 (d, J=8.2 Hz, 1 H, H-4), 6.73 (d, J=2.2 Hz, 1 H, H-7), 6.22 (dd, J=8.2, 2.2 Hz, 1 H, H-5), 4.47 (s, 2 H, NCH2Ar), 4.03 (dd, J=10.8, 8.8 Hz, 1 H, CHHN), 3.92 (dd, J=10.8, 4.6 Hz, 1 H, CHHN), 3.69 (dd, J=10.4, 4.1 Hz, 1 H, CHHCl), 3.67-3.60 (m, 1 H, H-3), 3.53 (dd, J=10.4, 7.9 Hz, 1 H, CHHCl), 2.83 (s, 3 H, NSO2CH3). 13C NMR a 148.7, 147.2, 146.8, 143.4, 119.9 (C-6,8,9,1,4), 127.8, 123.9 (C-2 and 6, 3 and 5), 125.7, 107.9, 98.6 (C-4,5,7), 54.6 (C-2), 47.5, 46.8 (CH2Cl, NCH2Ar), 41.9 (C-3), 34.5 (SO2CH3). MS (DEI, 35Cl) m/z 395 (35%, M+), 346 (100%, M-CH2Cl); HRMS calcd. for C17H18ClN3O4S 395.07066, found 395.06880.

Workup

  1. distillationslowly distilled off over 40 min
  2. customevaporated
  3. additionThe residue was diluted with water
  4. extractionextracted with EtOAc (×2)
  5. dry with materialthe extracts dried (Na2SO4)
  6. customevaporated
  7. customDry column chromatography
  8. washeluting with EtOAc/petroleum ether (1:2)

Sources & evidence

ORD record
ord-f7edfc0a56f948478a0104094ab39011
Source dataset
uspto-grants-2000_06
Patent number
US06071908

Reaction notes

Loading…