Triethylamine → HCID 67282546, compound

HRID 1910705Notes

Reaction equation

HRID 1910705 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N: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)[CH2:4][CH2:3]1.[C:33]([NH:40][CH2:41][C:42](O)=[O:43])([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[Cl:32][C:30]1[CH:29]=[CH:28][C:10]2[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]=[C:8]([N:5]3[CH2:4][CH2:3][CH:2]([NH:1][C:42](=[O:43])[CH2:41][NH:40][C:33](=[O:34])[O:35][C:36]([CH3:37])([CH3:38])[CH3:39])[CH2:7][CH2:6]3)[C:9]=2[CH:31]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 78288N-(tert-butoxycarbonyl)glycineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67282603HCID 67282603, compound

Product 1

HCID 67282546HCID 67282546, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-(4-Aminopiperidin-1-yl)-7-chloro-1-methyl-3-(naphthalen-2-ylmethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (15 mg, 0.034 mmol) was dissolved in anhydrous N,N-dimethylformamide (0.3 mL), and Boc-glycine (7 mg, 0.037 mmol), and then 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride (8 mg, 0.04 mmol), 1-hydroxybenztriazole (5 mg, 0.04 mmol), and triethylamine (6 μL, 0.04 mmol) were added. The reaction was stirred at ambient temperature for 24 hours. The solution was diluted with ethyl acetate (5 mL), washed with saturated sodium bicarbonate (3×1 mL), dried with sodium sulfate, decanted and concentrated in vacuo. Column chromatography eluting with a gradient of 70-100% ethyl acetate in hexanes provided tert-butyl 2-(1-(7-chloro-1-methyl-3-(naphthalen-2-ylmethyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)piperidin-4-ylamino)-2-oxoethylcarbamate (3 mg, 15%). This material was dissolved in dichloromethane (0.2 mL) and trifluoroacetic acid (0.1 mL) and stirred at ambient temperature for 1 hour then concentrate in vacuo. Azeotroping four times with dichloromethane provided 2-amino-N-(1-(7-chloro-1-methyl-3-(naphthalen-2-ylmethyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-5-yl)piperidin-4-yl)acetamide as the trifluoroacetate salt (3 mg, quant. yield). ESI m/z measured 504.2173 [M+H]+. calculated 504.2166.

Workup

  1. washwashed with saturated sodium bicarbonate (3×1 mL)
  2. dry with materialdried with sodium sulfate
  3. customdecanted
  4. concentrationconcentrated in vacuo
  5. washColumn chromatography eluting with a gradient of 70-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d0fbed5266e643eeb780dec2659fa7bf
Source dataset
uspto-grants-2013_12
Patent number
US08604023B2

Reaction notes

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