Diisopropylethylamine → Methyl(1s,4s,5s,7s,10s)-4-benzyl-1,10-di-tert-butyl-5-hydroxy-2,9,12-trioxo-7-[4-(1,3-thiazol-2-yl)benzyl]-13-oxa-3,8,11-triazatetradec-1-ylcarbamate

HRID 1174363Notes

Reaction equation

HRID 1174363 reaction equation
[NH2:1][C@@H:2]([CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C@@H:3]([OH:31])[CH2:4][C@@H:5]([NH:18][C:19](=[O:30])[C@H:20]([C:26]([CH3:29])([CH3:28])[CH3:27])[NH:21][C:22]([O:24][CH3:25])=[O:23])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:14][CH:15]=[CH:16][N:17]=2)=[CH:9][CH:8]=1.[CH3:39][O:40][C:41]([NH:43][C@@H:44]([C:48]([CH3:51])([CH3:50])[CH3:49])[C:45](O)=[O:46])=[O:42].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>O1CCCC1>[CH3:39][O:40][C:41](=[O:42])[NH:43][C@@H:44]([C:48]([CH3:50])([CH3:49])[CH3:51])[C:45](=[O:46])[NH:1][C@@H:2]([CH2:32][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[C@@H:3]([OH:31])[CH2:4][C@H:5]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:14][CH:15]=[CH:16][N:17]=2)=[CH:9][CH:8]=1)[NH:18][C:19](=[O:30])[C@H:20]([C:26]([CH3:29])([CH3:28])[CH3:27])[NH:21][C:22](=[O:23])[O:24][CH3:25]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 11263950N-(Methoxycarbonyl)-L-tert-leucineHCID 67407704N1-{(1S,3S,4S)-4-amino-3-hydroxy-5-phenyl-1-[4-(1,3-thiazol-2-yl)benzyl]pentyl}-N2-(methoxycarbonyl)-3-methyl-L-valinamide

Product 1

HCID 11320048Methyl(1s,4s,5s,7s,10s)-4-benzyl-1,10-di-tert-butyl-5-hydroxy-2,9,12-trioxo-7-[4-(1,3-thiazol-2-yl)benzyl]-13-oxa-3,8,11-triazatetradec-1-ylcarbamateYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution containing the product from Example 146C (0.035 g, 0.065 mmol) in tetrahydrofuran (0.70 mL) were added the product from Example 1F (0.012 g, 0.063 mmol), DEPBT (0.029 g, 0.097 mmol), and N,N-diisopropylethylamine (0.056 mL, 0.321 mmol) and the mixture was stirred at room temperature for 3 hours. 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 reverse phase HPLC on a C18 column, eluting with a gradient starting with water (containing 0.1% trifluoroacetic acid) and ending with acetonitrile to give the product (0.021 g, 46% yield). 1H NMR (300 MHz, MeOH-d6), δ ppm 0.86 (s, 9 H), 0.88 (s, 9 H), 1.61-1.71 (m, 2 H), 2.58-2.65 (m, 1 H), 2.76-2.96 (m, 4 H), 3.57 (s, 3H), 3.65 (s, 3 H), 3.74-3.79 (m, 1 H), 3.81 (s, 1 H), 3.1 (s, 1 H), 4.19-4.28 (m, 1 H), 4.30-4.40 (m, 1 H), 7.10-7.28 (m, 7 H), 7.56 (d, J=3.3 Hz, 1 H), 7.78 (d, J=8.1 Hz, 2 H), 7.83 (d, J=3.3 Hz, 1 H).

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 reverse phase HPLC on a C18 column
  7. washeluting with a gradient

Sources & evidence

ORD record
ord-2eec5f0e18294a9faced6c4d1549f501
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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