1-Hydroxybenzotriazole → HCID 24801479, compound

HRID 469810Notes

Reaction equation

HRID 469810 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:13][C:14]2[O:15][C:16]3[C:22]([C:23]4[CH:24]=[C:25]([C:28](O)=[O:29])[S:26][CH:27]=4)=[CH:21][CH:20]=[CH:19][C:17]=3[N:18]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].C[CH2:32][N:33]=C=NCCCN(C)C.Cl.CN.C1COCC1.C1C=CC2N(O)N=NC=2C=1>CN(C1C=CN=CC=1)C.CCOC(C)=O.ClCCl>[CH3:32][NH:33][C:28]([C:25]1[S:26][CH:27]=[C:23]([C:22]2[C:16]3[O:15][C:14]([NH:13][C:5]4[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=4)=[N:18][C:17]=3[CH:19]=[CH:20][CH:21]=2)[CH:24]=1)=[O:29]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66615946Methylamine tetrahydrofuranHCID 67457210HCID 67457210, compound

Product 1

HCID 24801479HCID 24801479, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 0.04 g (0.083 mmol) 4-[2-(3,4,5-trimethoxy-phenylamino)-benzooxazol-7-yl]-thiophene-2-carboxylic acid, 0.025 g (0.127 mmol) EDC-HCl, 0.016 g (0.128 mmol) DMAP, 0.83 ml (1.7 mmol) methylamine THF solution (2M), 0.012 g (0.088 mmol) HOBt and 4 ml dichloromethane is stirred at room temperature for 72 h. Then EtOAc is added to the reaction mixture and the organic layer is washed with water (2×), dried over MgSO4, filtered and the filtrate is concentrated in vacuo. The residue is purified by chromatography (silicagel, hexane:EtOAc=1:2), followed by crystallization from dichloromethane/diethyl ether to afford the title compound as off-white crystals. Rt=2.15 min (Waters Symmetry C8, 2.1×50 mm, detection 210-250 nM, 5% to 100% CH3CN in H2O in 2 min+0.05% TFA, flow rate 1.0 ml/min); MS: 440 (M+1)+; m.p. 260-262° C.

Workup

  1. washthe organic layer is washed with water (2×)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationthe filtrate is concentrated in vacuo
  5. customThe residue is purified by chromatography (silicagel, hexane:EtOAc=1:2)
  6. customfollowed by crystallization from dichloromethane/diethyl ether

Sources & evidence

ORD record
ord-f7ab31d697284973908aa77863a00dc9
Source dataset
uspto-grants-2014_01
Patent number
US08629168B2

Reaction notes

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