Triethylamine → tert-butyl N-(4-[[(3S)-3-[(ethylcarbamoyl)methyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate

HRID 1503907Notes

Reaction equation

HRID 1503907 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:32])[CH:9]1[CH2:14][CH2:13][CH:12]([O:15][C:16]2[C:27]3[C:26]4[C@H:25]([CH2:28][C:29]([OH:31])=O)[CH2:24][CH2:23][C:22]=4[S:21][C:20]=3[N:19]=[CH:18][N:17]=2)[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=C[C:36]2N(O)N=[N:39][C:37]=2C=1.CCN=C=NCCCN(C)C.Cl.C(N)C.C(N(CC)CC)C>CN(C=O)C>[CH2:37]([NH:39][C:29]([CH2:28][C@@H:25]1[CH2:24][CH2:23][C:22]2[S:21][C:20]3[N:19]=[CH:18][N:17]=[C:16]([O:15][CH:12]4[CH2:13][CH2:14][CH:9]([N:8]([CH3:32])[C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH2:10][CH2:11]4)[C:27]=3[C:26]1=2)=[O:31])[CH3:36]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 11198Ethylamine hydrochlorideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 681154802-[(3S)-12-[(4-[[(tert-butoxy)carbonyl](methyl)amino]cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetic acid

Product 1

HCID 86695087tert-butyl N-(4-[[(3S)-3-[(ethylcarbamoyl)methyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamateYield 78.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 25-mL round-bottom flask was charged with intermediate 22.4 (200 mg, 0.43 mmol, 1.00 equiv), HOBt (90 mg, 0.67 mmol, 1.54 equiv), EDCI (191 mg, 1.00 mmol, 2.31 equiv), ethanamine hydrochloride (45 mg, 0.55 mmol, 1.27 equiv), triethylamine (135 mg, 1.34 mmol, 3.08 equiv) and 10 mL of distilled DMF. The resulting solution was stirred for 4 h at room temperature under nitrogen. The reaction was then quenched with water and extracted with 3×25 mL of ethyl acetate. The combined organic layers were washed with brine and dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was loaded onto a silica gel column with ethyl acetate/petroleum ether (1:2 to 3:5) and purified to provide the desired tert-butyl N-(4-[[(3S)-3-[(ethylcarbamoyl)methyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (24.1, 165 mg, 78%) as a white solid. MS: m/z 470 (M+H)+.

Workup

  1. customThe reaction was then quenched with water
  2. extractionextracted with 3×25 mL of ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationAfter filtration and concentration under reduced pressure
  6. custompurified

Sources & evidence

ORD record
ord-126426b5469e4ff3a6470aea543bad2b
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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