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]-1-ethylcyclohexyl)carbamate

HRID 1503980Notes

Reaction equation

HRID 1503980 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([CH2:32][CH3:33])[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=O)C.CN(C)C1C=CN=CC=1>[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][C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:4])[CH3:3])([CH2:32][CH3:33])[CH2:10][CH2:11]4)[C:27]=3[C:26]1=2)(=[O:31])[NH2:40]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 866951402-[(3R)-12-[(4-[[(tert-butoxy)carbonyl]amino]-4-ethylcyclohexyl)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 68115474tert-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]-1-ethylcyclohexyl)carbamateYield 60.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 2-[(3R)-12-[(4-[[(tert-butoxy)carbonyl]amino]-4-ethylcyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetic acid (100 mg, 0.21 mmol, 1.00 equiv) in 5 mL of distilled DMF was added HOBt (42.6 mg), EDCI (60 mg), 4-dimethylaminopyridine (38.2 mg) and NH4Cl (56 mg, 1.05 mmol, 4.98 equiv) successively and the resulting solution was stirred for 14 hr at 25° C. under nitrogen. The reaction was then quenched with water and extracted with 3×50 mL of ethyl acetate. The organic layers were combined, washed with brine, dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (2:1) to give 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]-1-ethylcyclohexyl)carbamate (60 mg, 60%) as colorless oil. MS (ES): m/z 476 [M+H]+.

Workup

  1. customThe reaction was then quenched with water
  2. extractionextracted with 3×50 mL of ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-d3266f2e906c42c4a894d94bdf95bfe1
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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