Dichloromethane → N,N'-bis-Boc-(2R)-2,5-diamino-N-[(1R)-1-[(RS)-(5-tert-butyl-2-benzoxazolyl)-hydroxymethyl]-3-phenylpropyl]-valeramide

HRID 2304867Notes

Reaction equation

HRID 2304867 reaction equation
[C:1]([C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11]([CH:13]([OH:24])[C@H:14]([NH2:23])[CH2:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:10][C:9]=2[CH:25]=1)([CH3:4])([CH3:3])[CH3:2].C([NH:33][C@@H:34]([C:46](O)=[O:47])[CH2:35][CH2:36][CH2:37][NH:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])(OC(C)(C)C)=O.Cl[CH2:50]Cl.C1CN([P+](Br)(N2[CH2:67][CH2:66][CH2:65]C2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[C:76]([O:79]CC)(=[O:78])C>C(N(CC)CC)C>[C:76]([N:23]([C@@H:14]([CH:13]([C:11]1[O:12][C:8]2[CH:7]=[CH:6][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:25][C:9]=2[N:10]=1)[OH:24])[CH2:15][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[C:46](=[O:47])[C@H:34]([NH2:33])[CH2:35][CH2:36][CH2:37][NH:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])([O:79][C:66]([CH3:65])([CH3:67])[CH3:50])=[O:78]

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 8857Ethyl AcetateHCID 2733179PyBroPHCID 7015801HCID 7015801, compoundHCID 57124382(1R)-1-[(RS)-(5-tert-Butyl-2-benzoxazolyl)hydroxymethl]-3-phenylpropylamine

Product 1

HCID 22961351N,N'-bis-Boc-(2R)-2,5-diamino-N-[(1R)-1-[(RS)-(5-tert-butyl-2-benzoxazolyl)-hydroxymethyl]-3-phenylpropyl]-valeramide

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (1R)-1-[(RS)-(5-tert-butyl-2-benzoxazolyl)hydroxymethyl]-3-phenylpropylamine (108 mg), N,N′-bis-Boc-D-ornithine (130 mg), dichloromethane (3 mL), PyBrop (164 mg) and triethylamine (195 μL) was stirred at 0° C. for 1 h, then at 25° C. for 10 h. The reaction mixture is poured into ethyl acetate, washed successively with water, 1 N HCl, saturated aqueous bicarbonate and brine. The organic layer is dried (Na2SO4), concentrated and the residue is purified by chromatography over silica gel (30% ethyl acetate/hexane) afforded N,N′-bis-Boc-(2R)-2,5-diamino-N-[(1R)-1-[(RS)-(5-tert-butyl-2-benzoxazolyl)-hydroxymethyl]-3-phenylpropyl]-valeramide (130 mg) which was deprotected (trifluoroacetic acid) to give the title product (107 mg) as a white powder: 1H NMR (300 MHz, D2O) δ 1.35 and 1.26 (2s, 9H), 1.54 (m, 2H), 1.85-2.19 (m, 2H), 2.77 (m, 4H), 4.79 (m, 1H), 4.42 (m, 1H), 5.02 (s, 0.2H), 5.14 (d, J=3.3 Hz, 0.8H), 7.21-7.38 (m, 5H), and 7.78 (m, 1H).

Workup

  1. waitat 25° C. for 10 h
  2. washwashed successively with water, 1 N HCl, saturated aqueous bicarbonate and brine
  3. dry with materialThe organic layer is dried (Na2SO4)
  4. concentrationconcentrated
  5. customthe residue is purified by chromatography over silica gel (30% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b1068f7d5c3a4bfca218437a8c356f9a
Source dataset
uspto-grants-2002_08
Patent number
US06436980B1

Reaction notes

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