1-Hydroxybenzotriazole → HCID 59784110, compound

HRID 2079760Notes

Reaction equation

HRID 2079760 reaction equation
[C@H:1]1([NH:11][C:12]([C@H:14]2[NH:19][CH2:18][CH2:17][N:16]([C:20]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:21])[CH2:15]2)=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[C:30]([NH:37][C@H:38]([C:42](O)=[O:43])[CH:39]([CH3:41])[CH3:40])([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[C:33]([O:32][C:30]([NH:37][C@@H:38]([CH:39]([CH3:41])[CH3:40])[C:42]([N:19]1[CH2:18][CH2:17][N:16]([C:20]([O:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[O:21])[CH2:15][C@H:14]1[C:12]([NH:11][C@H:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1)=[O:13])=[O:43])=[O:31])([CH3:36])([CH3:35])[CH3:34]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 83693Boc-L-ValineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59440290HCID 59440290, compound

Product 1

HCID 59784110HCID 59784110, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The deprotected piperazine 3 (16.20 g, 41.2 mmol) is coupled with BOC-L-valine (8.95 g, 41.2 mmol) using DIEA (36.0 mL, 0.21 mol), HBTU (17.19 g, 45.3 mmol) and HOBt (6.12 g, 45.3 mmol) in DMF (700 mL) under the same conditions as in step 1 above. Purification is carried out by flash chromatography on silica gel (CH2Cl2 as eluent initially, followed by 10% Et2O/CH2Cl2 to elute the desired product). The desired coupled product 4 is isolated as a white foam (15.51 g, 64% yield): 1H NMR δ (CDCl3) 6.99-7.64 (m, 9H), 5.99-6.34 (br m, 1H), 2.68-5.26 (br m, 11H), 1.51-2.15 (br m, 6H), 1.42 (s, 9H), 1.15 (s, 3H), 0.64-1.02 (br m, 5H); LCMS (APCl+) 594.2 (MH+), 537.9 (MH+-tBu), 493.7 (MH+-BOC, 100%).

Workup

  1. customPurification
  2. washto elute the desired product)

Sources & evidence

ORD record
ord-eb9f8e8e05a4414e899a4b13f3f4887e
Source dataset
uspto-grants-2011_04
Patent number
US07932255B2

Reaction notes

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