1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 68345473, compound

HRID 1807575Notes

Reaction equation

HRID 1807575 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])[C:6]([OH:8])=O)#[N:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.O[NH:38][C:39]([C:41]1[CH:50]=[CH:49][CH:48]=[C:47]2[C:42]=1[CH2:43][CH2:44][CH2:45][C@@H:46]2[NH:51][C:52](=[O:58])[O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[NH:40]>CN(C=O)C.CC(=O)OCC>[C:1]([C:3]1[CH:4]=[C:5]([C:6]2[O:8][N:40]=[C:39]([C:41]3[CH:50]=[CH:49][CH:48]=[C:47]4[C:42]=3[CH2:43][CH2:44][CH2:45][C@@H:46]4[NH:51][C:52](=[O:58])[O:53][C:54]([CH3:56])([CH3:55])[CH3:57])[N:38]=2)[CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])#[N:2]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 21956832RP-101124HCID 178453867tert-butyl N-[(1S)-5-[(E)-N'-hydroxycarbamimidoyl]-1,2,3,4-tetrahydronaphthalen-1-yl]carbamate

Product 1

HCID 68345473HCID 68345473, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Prepared using General Procedure 2. To a stirring solution of 3-cyano-4-isopropoxybenzoic acid (556 mg, 2.72 mmol) in DMF (10 mL) was added HOBt (476.6 mg, 3.53 mmol) and EDCI (677.9 mg, 3.53 mmol). After stirring for 30 min, (S)-tert-butyl (5-(N-hydroxycarbamimidoyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate INT-10 (3.56 g crude, approximately 2.99 mmol) was added. After stirring at room temperature for an additional 90 min, the mixture was heated to 90° C. for 15 h. The mixture was diluted with EA and washed with NaHCO3. The combined organic layers were dried, concentrated, and chromatographed (EA/hexanes) to provide 1.89 g (46%) (S)-tert-butyl (5-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate INT-12 as a white solid. LCMS-ESI (m/z) calculated for C27H30N4O4: 474.6; no M/Z observed, tR=4.23 min. 1H NMR (400 MHz, CDCl3) δ 8.42 (d, J=2.1 Hz, 1H), 8.33 (dd, J=8.9, 2.2 Hz, 1H), 7.92 (dd, J=7.7, 1.1 Hz, 1H), 7.56 (d, J=7.6 Hz, 1H), 7.32 (dd, J=20.3, 12.6 Hz, 1H), 7.12 (d, J=9.0 Hz, 1H), 4.94 (d, J=6.0 Hz, 1H), 4.88-4.72 (m, 1H), 3.23-3.08 (m, 1H), 3.07-2.94 (m, 1H), 2.06 (d, J=12.6 Hz, 1H), 1.97-1.78 (m, 3H), 1.53-1.43 (m, 15H). 13C NMR (101 MHz, CDCl3) δ 172.64, 169.40, 162.69, 155.43, 138.65, 137.55, 134.04, 133.83, 131.68, 129.55, 126.08, 125.97, 116.74, 115.20, 113.53, 103.87, 79.44, 72.69, 48.97, 29.73, 28.40, 21.68, 19.71, 14.14.

Workup

  1. customPrepared
  2. stirringAfter stirring at room temperature for an additional 90 min
  3. washwashed with NaHCO3
  4. customThe combined organic layers were dried
  5. concentrationconcentrated
  6. customchromatographed (EA/hexanes)

Sources & evidence

ORD record
ord-1044ecf674e349098a5b58e7bf4635d7
Source dataset
uspto-grants-2013_01
Patent number
US08357706B2

Reaction notes

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