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

HRID 718906Notes

Reaction equation

HRID 718906 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:28]([O:30][CH2:31][CH:32]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:38]2[C:33]1=[CH:34][CH:35]=[CH:36][CH:37]=2)=[O:29])[C@H:23]([C:25](O)=[O:26])[CH3:24].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:25](=[O:26])[C@@H:23]([NH:22][C:28](=[O:29])[O:30][CH2:31][CH:32]1[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:38]=2[C:39]2[C:44]1=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH3:24])[CH3:6])[CH3:2]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 6364642N-((9H-Fluoren-9-ylmethoxy)carbonyl)-L-alanineHCID 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 86652578(9H-Fluoren-9-yl)methyl (S)-1-(((S)-1,1-diethoxypropan-2-yl)(quinolin-8-ylmethyl)amino)-1-oxopropan-2-ylcarbamateYield 69.1%

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-Ala-OH 18.3 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 18.1 g, (yield 69%).

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-17bfbd0043fd46169e4b49df9d2600ee
Source dataset
uspto-grants-2015_11
Patent number
US09193734B2

Reaction notes

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