1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86675867, compound

HRID 1895794Notes

Reaction equation

HRID 1895794 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:40]([CH3:42])[CH3:41])[C:10]([NH:12][C@@H:13]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])[CH:27]=1)[C:14]([N:16]1[CH2:21][CH2:20][CH2:19][C@@H:18]([C:22]([OH:24])=[O:23])[NH:17]1)=[O:15])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:43]([C:45]1[CH:53]=[C:52]2[C:48]([CH2:49][CH2:50][C@H:51]2O)=[CH:47][CH:46]=1)=[CH2:44].C(N=C=NCCCN(C)C)C>CN(C)C1C=CN=CC=1.ClCCl>[CH:43]([C:45]1[CH:53]=[C:52]2[C:48]([CH2:49][CH2:50][C@H:51]2[O:23][C:22]([C@@H:18]2[CH2:19][CH2:20][CH2:21][N:16]([C:14](=[O:15])[C@@H:13]([NH:12][C:10](=[O:11])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH:40]([CH3:42])[CH3:41])[CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:34])[CH3:35])[CH:27]=3)[NH:17]2)=[O:24])=[CH:47][CH:46]=1)=[CH2:44]

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 67957573HCID 67957573, compoundHCID 67957629HCID 67957629, compound

Product 1

HCID 86675867HCID 86675867, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-1-{(S)-2-((S)-2-tert-butoxycarbonylamino-3-methyl-butyrylamino)-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionyl}-hexahydro-pyridazine-3-carboxylic acid (658 mg, 1.086 mmol) 2f, prepared as described earlier, (R)-6-vinyl-indan-1-ol (208.7 mg, 1.303 mmol) and 4-dimethylaminopyridine (132.7 mg, 1.086 mmol) in anhydrous dichloromethane (20 mL) was treated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (340.6 mg, 1.738 mmol). After overnight stirring at room temperature the volatiles were removed in vacuo and the residue was purified by silica gel chromatography using a 50 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 1:1 to afford the title compound (762 mg, 95%) as a white solid. 1H NMR (300 MHz, CDCl3) δ0.13-0.22 (m, 6H), 0.86-0.99 (m, 15H), 1.47 (s, 10H), 1.72-1.91 (m, 3H), 1.99-2.20 (m, 2H), 2.43-2.60 (m, 2H), 2.66-2.78 (m, 1H), 2.81-3.01 (m, 3H), 3.04-3.17 (m, 1H), 3.91-4.01 (m, 1H), 4.33 (br d, J=12.7 Hz, 1H), 5.03-5.11 (m, 1H), 5.22-5.33 (m, 1H), 5.70-5.82 (m, 2H), 6.21 (dd, J=3.6, 6.9 Hz, 1H), 6.49 (d, J=8.5 Hz, 1H), 6.57-6.65 (m, 2H), 6.68-6.74 (m, 1H), 6.75-6.85 (m, 2H), 6.92 (app t, J=7.6 Hz, 1H), 7.26 (d, J=7.8 Hz, 1H), 7.41 (d, J=7.8 Hz, 1H), 7.48 (s, 1H). LCMS (m/z) 771.4 [M+Na], Tr=6.05 min.

Workup

  1. customwere removed in vacuo
  2. customthe residue was purified by silica gel chromatography
  3. washeluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 1:1

Sources & evidence

ORD record
ord-d41711822fd14884a161b9d406c04e7c
Source dataset
uspto-grants-2013_08
Patent number
US08513184B2

Reaction notes

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