Triethylamine → di(tert-butyl) 2-({[1-(chloromethyl)-5-nitro-1,2-dihydro-3H-benzo[e]indol-7-yl]sulfonyl}amino)ethyl phosphate

HRID 2238448Notes

Reaction equation

HRID 2238448 reaction equation
[P:1]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])([O:3][CH2:4][CH2:5][NH2:6])=[O:2].CCN(CC)CC.[Cl:24][CH2:25][CH:26]1[C:34]2[C:33]3[CH:35]=[CH:36][C:37]([S:39](Cl)(=[O:41])=[O:40])=[CH:38][C:32]=3[C:31]([N+:43]([O-:45])=[O:44])=[CH:30][C:29]=2[N:28](C(=O)C(F)(F)F)[CH2:27]1.C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.O.CO>[P:1]([O:3][CH2:4][CH2:5][NH:6][S:39]([C:37]1[CH:36]=[CH:35][C:33]2[C:34]3[CH:26]([CH2:25][Cl:24])[CH2:27][NH:28][C:29]=3[CH:30]=[C:31]([N+:43]([O-:45])=[O:44])[C:32]=2[CH:38]=1)(=[O:41])=[O:40])([O:7][C:8]([CH3:10])([CH3:9])[CH3:11])([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:2]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 862404572-Aminoethyl di(tert-butyl) phosphateHCID 866202591-(chloromethyl)-5-nitro-3-(trifluoroacetyl)-1,2-dihydro-3H-benzo[e]indole-7-sulfonyl chloride

Product 1

HCID 54762391di(tert-butyl) 2-({[1-(chloromethyl)-5-nitro-1,2-dihydro-3H-benzo[e]indol-7-yl]sulfonyl}amino)ethyl phosphateYield 91%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of amine 226 (203 mg, 0.80 mmol) and Et3N (0.11 mL, 0.80 mmol) in THF (2 mL) was added to solution of 116 (306 mg, 0.67 mmol) in THF (8 mL) at 0° C. After 5 min the cooling bath was removed and after 10 min Cs2CO3 (0.44 g, 1.3 mmol) and MeOH (4 mL) were added. After a further 25 min the mixture was diluted with water and extracted with CH2C2 (×3). The combined extracts were dried and evaporated and the residue was purified by chromatography, eluting with EtOAc/petroleum ether (1:1 then 2:1) to give di(tert-butyl) 2-({[1-(chloromethyl)-5-nitro-1,2-dihydro-3H-benzo[e]indol-7-yl]sulfonyl}amino)ethyl phosphate (227) (351 mg, 91%) as a red-orange foam: 1H NMR [(CD3)2SO] δ 8.59 (d, J=1.6 Hz, 1H), 8.04 (d, J=8.9 Hz, 1H), 7.95 (br s, 1H, 7.79 (dd, J=8.9, 1.8 Hz, 1H, 7.77 (s, 1H), 6.74 (s, 1H), 4.28-4.20 (m, 1H), 3.95-3.86 (m, 2H), 3.83-3.72 (m, 4H), 2.99 (t, J=6.0 Hz, 2H), 1.35 (s, 18H). HMS (FAB) calcd. for C23H3335ClN3O8PS (M+) m/z 577.1415, found 577.1412.

Workup

  1. additionwere added
  2. extractionextracted with CH2C2 (×3)
  3. customThe combined extracts were dried
  4. customevaporated
  5. customthe residue was purified by chromatography
  6. washeluting with EtOAc/petroleum ether (1:1

Sources & evidence

ORD record
ord-a7804a1ec06b464ea2a9f008cc03ca20
Source dataset
uspto-grants-2010_05
Patent number
US07718688B2

Reaction notes

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