1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl N-(4-[[(3R)-3-(carbamoylmethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-ethylcarbamate

HRID 1503957Notes

Reaction equation

HRID 1503957 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:32][CH3:33])[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=CC2N(O)N=[N:40]C=2C=1.CCN=C=NCCCN(C)C.[NH4+].[Cl-]>CN(C)C1C=CN=CC=1.CN(C=O)C.O>[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[CH2:11][CH2:10][CH:9]([N:8]([CH2:32][CH3:33])[C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH2:14][CH2:13]4)[C:27]=3[C:26]1=2)(=[O:31])[NH2:40]

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 681155382-[(3R)-12-[(4-[[(tert-butoxy)carbonyl](ethyl)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 68115477tert-butyl N-(4-[[(3R)-3-(carbamoylmethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-ethylcarbamateYield 74.6%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A 50-mL round-bottom flask was charged with a solution of 2-[(3R)-12-[(4-[[(tert-butoxy)carbonyl](ethyl)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 (310 mg, 0.65 mmol, 1.00 equiv), HOBt (132 mg), EDCI (186.9 mg), 4-dimethylaminopyridine (118 mg) and NH4Cl (209 mg, 3.91 mmol, 5.99 equiv) in distilled DMF (6 mL). The solution was stirred for 14 hrs at 25° C. under nitrogen. The resulting solution was diluted with water and extracted with 3×50 mL of ethyl acetate. The combined organic layers were washed with 3×20 mL of brine, dried over sodium and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (2:1) to afford tert-butyl N-(4-[[(3R)-3-(carbamoylmethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-ethylcarbamate (230 mg, 74%) as a colorless oil. MS (ES): m/z 475 [M+H]+.

Workup

  1. extractionextracted with 3×50 mL of ethyl acetate
  2. washThe combined organic layers were washed with 3×20 mL of brine
  3. dry with materialdried over sodium
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-a6882814567d49a38109e085b12928c4
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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