Diisopropylethylamine → N1-{(1S,3S,4S)-4-[(tert-butoxycarbonyl)amino]-3-{[tert-butyl(dimethyl)silyl]oxy}-5-phenyl-1-[4-(1,3-thiazol-2-yl)benzyl]pentyl}-N2-(methoxycarbonyl)-3-methyl-L-valinamide

HRID 1174361Notes

Reaction equation

HRID 1174361 reaction equation
[NH2:1][C@@H:2]([CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]2[S:37][CH:38]=[CH:39][N:40]=2)=[CH:32][CH:31]=1)[CH2:3][C@H:4]([O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[C@@H:5]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:41][O:42][C:43]([NH:45][C@@H:46]([C:50]([CH3:53])([CH3:52])[CH3:51])[C:47](O)=[O:48])=[O:44].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>O1CCCC1>[C:16]([O:15][C:14]([NH:13][C@@H:5]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C@@H:4]([O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH2:3][C@@H:2]([NH:1][C:47](=[O:48])[C@H:46]([C:50]([CH3:52])([CH3:51])[CH3:53])[NH:45][C:43]([O:42][CH3:41])=[O:44])[CH2:29][C:30]1[CH:31]=[CH:32][C:33]([C:36]2[S:37][CH:38]=[CH:39][N:40]=2)=[CH:34][CH:35]=1)=[O:20])([CH3:17])([CH3:18])[CH3:19]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 11263950N-(Methoxycarbonyl)-L-tert-leucineHCID 86726241tert-butyl (1S,2S,4S)-4-amino-1-benzyl-2-{[tert-butyl(dimethyl)silyl]oxy}-5-[4-(1,3-thiazol-2-yl)phenyl]pentylcarbamate

Product 1

HCID 68510354N1-{(1S,3S,4S)-4-[(tert-butoxycarbonyl)amino]-3-{[tert-butyl(dimethyl)silyl]oxy}-5-phenyl-1-[4-(1,3-thiazol-2-yl)benzyl]pentyl}-N2-(methoxycarbonyl)-3-methyl-L-valinamideYield 70.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution containing the product from Example 146A (0.053 g) in tetrahydrofuran (0.70 mL) were added the product from Example 1F (0.015 g, 0.079 mmol), DEPBT (0.033 g, 0.110 mmol), and N,N-diisopropylethylamine (0.065 mL, 0.373 mmol) and the mixture was stirred at room temperature for 1 hour. The mixture was partitioned between ethyl acetate and 10% Na2CO3 solution. The organic was washed with additional 10% Na2CO3 solution and then brine, dried over MgSO4, filtered and evaporated. The residue was chromatographed on silica gel eluting with a gradient starting with chloroform and ending with 80 % ethyl acetate in chloroform to give the product (0.042 g).

Workup

  1. customThe mixture was partitioned between ethyl acetate and 10% Na2CO3 solution
  2. washThe organic was washed with additional 10% Na2CO3 solution
  3. dry with materialbrine, dried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was chromatographed on silica gel eluting with a gradient

Sources & evidence

ORD record
ord-5e514ec02bd441ad8bd3934f25edbc65
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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