Diisopropylethylamine → (9H-Fluoren-9-yl)methyl(S)-1-(((S)-1,1-diethoxypropan-2-yl)(quinolin-8-ylmethyl)amino)-1,4-dioxo-4-(tritylamino)butan-2-ylcarbamate

HRID 1254509Notes

Reaction equation

HRID 1254509 reaction equation
[CH2:1]([O:3][CH:4]([O:19][CH2:20][CH3:21])[C@@H:5]([NH:7][CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[CH:16][CH:15]=[CH:14]2)[CH3:6])[CH3:2].[NH:22]([C:50]([O:52][CH2:53][CH:54]1[C:66]2[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=2)[C:60]2[C:55]1=[CH:56][CH:57]=[CH:58][CH:59]=2)=[O:51])[C@H:23]([C:47](O)=[O:48])[CH2:24][C:25](=[O:46])[NH:26][C:27]([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CC(=O)OCC.O>[CH2:1]([O:3][CH:4]([O:19][CH2:20][CH3:21])[C@@H:5]([N:7]([CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[CH:16][CH:15]=[CH:14]2)[C:47](=[O:48])[C@@H:23]([NH:22][C:50](=[O:51])[O:52][CH2:53][CH:54]1[C:66]2[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=2[C:60]2[C:55]1=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH2:24][C:25](=[O:46])[NH:26][C:27]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH3:6])[CH3:2]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 640248Fmoc-Asn(Trt)-OHHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67074994(S)-1,1-diethoxy-N-(quinolin-8-ylmethyl)propan-2-amine

Product 1

HCID 86698535(9H-Fluoren-9-yl)methyl(S)-1-(((S)-1,1-diethoxypropan-2-yl)(quinolin-8-ylmethyl)amino)-1,4-dioxo-4-(tritylamino)butan-2-ylcarbamateYield 66.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

According to the procedure described in the synthesis method of Compound III-1, (S)-1,1-diethoxy-N-(quinolin-8-ylmethyl)propan-2-amine (Compound IX-3) 13.0 g (45 mmol) and Fmoc-Asn(Trt)-OH 35.1 g (58.8 mmol) were dissolved in DMF (200 ml). HATU (25.6 g, 67.5 mmol) and DIEA (8.7 g, 67.5 mmol) were added at room temperature. The mixture was stirred overnight at room temperature. The mixture was poured into water (800 ml). The solution was extracted with EA (300 ml×3). The combined extracts were dried over Na2SO4 and then filtered. The solvent was removed in vacuo. The residue was purified by column chromatography on silica gel with PE:EA=30:1 to 5:1 to give the title compound 25.8 g, (yield 66%).

Workup

  1. extractionThe solution was extracted with EA (300 ml×3)
  2. dry with materialThe combined extracts were dried over Na2SO4
  3. filtrationfiltered
  4. customThe solvent was removed in vacuo
  5. customThe residue was purified by column chromatography on silica gel with PE

Sources & evidence

ORD record
ord-41e74de320d04a7c86758f50197d42e8
Source dataset
uspto-grants-2013_06
Patent number
US08455488B2

Reaction notes

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