Tetrahydrofuran → 3-{[tert-Butoxycarbonyl-(4-morpholin-4-yl-phenyl)-amino]-methyl}1H-indole-6-carboxylic acid methyl ester

HRID 852924Notes

Reaction equation

HRID 852924 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([C:9]([CH2:14][NH:15][C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)=[CH:18][CH:17]=3)=[CH:10][NH:11]2)=[CH:7][CH:6]=1)=[O:4].C1COCC1.[O:33](C(OC(C)(C)C)=O)[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=O>>[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([C:9]([CH2:14][N:15]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:33])[C:16]3[CH:17]=[CH:18][C:19]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)=[CH:20][CH:21]=3)=[CH:10][NH:11]2)=[CH:7][CH:6]=1)=[O:4]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 90495Di-tert-butyl dicarbonateHCID 589306603-[(4-Morpholin-4-yl-phenylamino)-methyl]1H-indole-6-carboxylic acid methyl ester

Product 1

HCID 589305773-{[tert-Butoxycarbonyl-(4-morpholin-4-yl-phenyl)-amino]-methyl}1H-indole-6-carboxylic acid methyl esterYield 79%

Procedure

To a solution of 123 (689 mg, 1.89 mmol) in THF (100 ml) Et3N (289 μl, 2.08 mmol) was added dropwise. (BOC)2O was added slowly and the mixture was stirred at room temperature overnight under nitrogen, THF was evaporated off and the residue was partitioned between water and CH2Cl2. Organic layer was separated, dried over MgSO4, evaporated to form another residue which was purified by flash column chromatography (EtOAc/hexane, 7:3) to afford the title compound 124 (692 mg, 79%). 1H-NMR (CDCl3) δ: 8.24 (m, 1H), 8.09 (m, 1H); 7.76 (dd, J=8.2, 1.4 Hz, 1H); 7.55 (d, J=8.8 Hz, 1H); 7.13 (d, J=2.5 Hz, 1H); 6.93 (m, 3H); 4.97 (s, 2H); 3.94 (s, 3H); 3.89 (m, 4H); 3.16 (m, 4H); 1.47 (s, 9H).

Workup

  1. customTHF was evaporated off
  2. customthe residue was partitioned between water and CH2Cl2
  3. customOrganic layer was separated
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customto form another residue which
  7. customwas purified by flash column chromatography (EtOAc/hexane, 7:3)

Sources & evidence

ORD record
ord-dc4def2e3535402c9ed386d8af04ddc9
Source dataset
uspto-grants-2007_08
Patent number
US07253204B2

Reaction notes

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