Triethylamine → HCID 46947037, compound

HRID 1910708Notes

Reaction equation

HRID 1910708 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[C:9]3[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:10]=3[N:11]([CH3:27])[C:12](=[O:26])[CH:13]([CH2:15][C:16]3[CH:25]=[CH:24][C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[CH:17]=3)[N:14]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:40]([O:43][CH2:44][C:45](Cl)=[O:46])(=[O:42])[CH3:41]>ClCCl>[C:40]([O:43][CH2:44][C:45]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:9]3[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:10]=3[N:11]([CH3:27])[C:12](=[O:26])[CH:13]([CH2:15][C:16]3[CH:25]=[CH:24][C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[CH:17]=3)[N:14]=2)=[CH:6][N:7]=1)=[O:46])(=[O:42])[CH3:41]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 26297Acetoxyacetyl chloride2×HCID 46946832HCID 46946832, compound

Product 1

HCID 46947037HCID 46947037, compoundYield 75.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-(6-Aminopyridin-3-yl)-7-chloro-1-methyl-3-(naphthalen-2-ylmethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (50 mg, 0.11 mmol) was dissolved in dichloromethane (0.5 mL), and triethylamine (19 μL, 0.14 mmol) was added followed by acetoxyacetyl chloride (13 μL, 0.12 mmol). A slightly exothermic reaction occurred. This mixture as stirred at ambient temperature overnight. Additional triethylamine (46 μL, 0.33 mmol) was added followed by acetoxyacetyl chloride (30 μL, 0.22 mmol) and stirring continued at ambient temperature for 4 days. Concentration in the presence of silica, then column chromatography eluting with a step gradient of 20-80% ethyl acetate in hexanes in 5% increments every 3 minutes provided 2-(5-(7-chloro-1-methyl-3-(naphthalen-2-ylmethyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)pyridin-2-ylamino)-2-oxoethyl acetate (45 mg, 73%). 1H NMR (300 MHz, d6-DMSO) δ 2.10 (s, 3H), 3.3 (s, 3H), 3.53 (d, 2H) 3.83 (t, 1H), 4.72 (s, 2H), 7.30 (m, 1H), 7.4-7.5 (m, 3H), 7.60 (m, 2H), 7.65 (m, 1H), 7.77-7.88 (m, 4H), 8.03 (m, 1H), 8.36, (m, 1H), 10.94 (s, 1H); ESI m/z measured 541.1646 [M+H]+. calculated 541.1643.

Workup

  1. customA slightly exothermic reaction
  2. stirringstirring
  3. waitcontinued at ambient temperature for 4 days
  4. concentrationConcentration in the presence of silica
  5. washcolumn chromatography eluting with a step gradient of 20-80% ethyl acetate in hexanes in 5% increments every 3 minutes

Sources & evidence

ORD record
ord-ca8c05d300124f148e252769fd7fae26
Source dataset
uspto-grants-2013_12
Patent number
US08604023B2

Reaction notes

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