1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 59704208, compound

HRID 2427481Notes

Reaction equation

HRID 2427481 reaction equation
[NH2:1][C:2]1[O:3][C:4]2[C:9]([C@@H:10]([C:14]3[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([Br:24])[CH:15]=3)[C:11]=1[C:12]#[N:13])=[CH:8][CH:7]=[C:6]([NH2:25])[C:5]=2[NH2:26].[NH:27]([C:33]([O:35][CH2:36][CH:37]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:43]2[C:38]1=[CH:39][CH:40]=[CH:41][CH:42]=2)=[O:34])[C@H:28]([C:30](O)=[O:31])[CH3:29].C1C=CC2N(O)N=NC=2C=1.C(N=C=NCCCN(C)C)C>CCOC(C)=O.CN(C)C=O>[NH2:1][C:2]1[O:3][C:4]2[C:9]([C@@H:10]([C:14]3[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([Br:24])[CH:15]=3)[C:11]=1[C:12]#[N:13])=[CH:8][CH:7]=[C:6]([NH:25][C:30]([C@@H:28]([NH:27][C:33](=[O:34])[O:35][CH2:36][CH:37]1[C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][C:43]=3[C:44]3[C:49]1=[CH:48][CH:47]=[CH:46][CH:45]=3)[CH3:29])=[O:31])[C:5]=2[NH2:26]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 6364642N-((9H-Fluoren-9-ylmethoxy)carbonyl)-L-alanineHCID 23649181Crolibulin

Product 1

HCID 59704208HCID 59704208, compoundYield 13.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To an oven-dried carousel reaction flask charged with a magnetic stir bar at room temperature under argon was added (R)-2,7,8-triamino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-chromene (0.200 g, 0.479 mmol), Fmoc-Ala-OH (0.179 g, 0.575 mmol), dimethylformamide (2.4 mL), HOBt 0.084 g, 0.62 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) (0.119 g, 0.623 mmol). The black solution was stirred at room temperature overnight. The solution was diluted with EtOAc (50 mL), washed with water (3×30 mL), brine (10 mL), dried over MgSO4, filtered and concentrated to give the crude product as a brown residue. Purification by flash column chromatography (silica gel 12 g pre-packed column, gradient elution with EtOAc:Hexanes, 1:9 to 1:4 to 1:1) gave 0.046 g (13%) of the title compound as a yellow solid: mp: 212-217° C. (dec); 1H-NMR (DMSO-d6): δ 9.37 (br s, 1H), 7.89 (d, J=7.7 Hz, 2H), 7.76-7.69 (m, 3H), 7.44-7.39 (m, 2H), 7.35-7.30 (m, 2H), 6.98 (d, J=1.9 Hz, 1H), 6.88 (br s, 2H), 6.88 (d, J=8.0 Hz, 1H), 6.86 (d, J=1.9 Hz, 1H), 6.31 (d, J=8.3 Hz, 1H), 4.79 (br s, 2H), 4.69 (s, 1H), 4.31-4.23 (m, 4H), 3.80 (s, 3H), 3.70 (s, 3H), 1.32 (d, J=6.9 Hz, 3H).

Workup

  1. customTo an oven-dried carousel reaction flask
  2. additioncharged with a magnetic stir bar at room temperature under argon
  3. washwashed with water (3×30 mL), brine (10 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude product as a brown residue
  8. customPurification
  9. washby flash column chromatography (silica gel 12 g pre-packed column, gradient elution with EtOAc:Hexanes, 1:9 to 1:4 to 1:1)

Sources & evidence

ORD record
ord-a42c043a80a544e9953cfba1c6e2128b
Source dataset
uspto-grants-2011_06
Patent number
US07968595B2

Reaction notes

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