Diisopropylethylamine → (9H-fluoren-9-yl)methyl (R)-3-((R)-2-dodecanamido-3-(hexadecyloxy)propylthio)-1-(1-(hydroxymethyl)cyclopropylamino)-1-oxopropan-2-ylcarbamate

HRID 2407873Notes

Reaction equation

HRID 2407873 reaction equation
[C:1]([NH:14][C@H:15]([CH2:41][O:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58])[CH2:16][S:17][CH2:18][C@@H:19]([C:38]([OH:40])=O)[NH:20][C:21](=[O:37])[O:22][CH2:23][CH:24]1[C:36]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:30]2[C:25]1=[CH:26][CH:27]=[CH:28][CH:29]=2)(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.[NH2:93][C:94]1([CH2:97][OH:98])[CH2:96][CH2:95]1>C(Cl)Cl>[C:1]([NH:14][C@H:15]([CH2:41][O:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58])[CH2:16][S:17][CH2:18][C@H:19]([NH:20][C:21](=[O:37])[O:22][CH2:23][CH:24]1[C:36]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:30]2[C:25]1=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:38]([NH:93][C:94]1([CH2:97][OH:98])[CH2:96][CH2:95]1)=[O:40])(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14146222(1-Aminocyclopropyl)methanol hydrochlorideHCID 71294499(5R,9R)-9-dodecanamido-1-(9H-fluoren-9-yl)-3-oxo-2,11-dioxa-7-thia-4-azaheptacosane-5-carboxylic acid

Product 1

HCID 86678277(9H-fluoren-9-yl)methyl (R)-3-((R)-2-dodecanamido-3-(hexadecyloxy)propylthio)-1-(1-(hydroxymethyl)cyclopropylamino)-1-oxopropan-2-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (5R,9R)-9-dodecanamido-1-(9H-fluoren-9-yl)-3-oxo-2,11-dioxa-7-thia-4-azaheptacosane-5-carboxylic acid (1 eq) and HBTU (1.2 eq) in DCM (0.06 M) was added DIEA (3.5 eq), followed by (1-aminocyclopropyl) methanol hydrochloride (1.2 eq). The reaction was stirred at room temperature for 2 hr. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 30-50% EtOAc/Hex to give (9H-fluoren-9-yl)methyl (R)-3-((R)-2-dodecanamido-3-(hexadecyloxy)propylthio)-1-(1-(hydroxymethyl)cyclopropylamino)-1-oxopropan-2-ylcarbamate.

Workup

  1. customThe crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record
ord-a9cac533bc884ab5b347109691b2e210
Source dataset
uspto-grants-2014_08
Patent number
US08808703B2

Reaction notes

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