Methanamine, N-methoxy-, hydrochloride (1:1) → [1-(Methoxy-methyl-carbamoyl)-2-(1-trityl-1H-imidazol-4-yl)-ethyl]-carbamic acid tert-butyl ester

HRID 852859Notes

Reaction equation

HRID 852859 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:13][C:14]1[N:15]=[CH:16][N:17]([C:19]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:18]=1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.Cl.[CH3:75][NH:76][O:77][CH3:78]>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([C:10](=[O:12])[N:76]([O:77][CH3:78])[CH3:75])[CH2:13][C:14]1[N:15]=[CH:16][N:17]([C:19]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:18]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 3437537N-Boc-N'-trityl-L-histidine

Product 1

HCID 86591138[1-(Methoxy-methyl-carbamoyl)-2-(1-trityl-1H-imidazol-4-yl)-ethyl]-carbamic acid tert-butyl esterYield 90.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-tert-Butoxycarbonylamino-3-(1-trityl-1H-imidazol-4-yl)-propionic acid (4.56 g, 9.18 mmol), DIPEA (3.55 g, 4.79 mL, 27.53 mmol), BOP (4.26 g, 9.63 mmol) and N,O-dimethylhydroxylamine hydrochloride (940 mg, 9.63 mmol) in DMF (100 mL) were stirred overnight. The DMF was removed and CH2Cl2 added. The solution was washed with dilute aqueous HCl (1M, 4X), water and brine. The solution was dried, filtered and the solvent removed. The product was chromatographed (silica gel, EA/PE, Rf 0.38 EA) to afford the title compound (4.475 g, 90.4%). ESMS 541 (M+H+) 1H NMR (500 MHz, CDCl3) δ 1.39 (9H, s), 2.92 (1H, dd, J=6.13, 14.45), 2.98 (1H, dd, J=5.63, 14.45), 3.13 (3H, s), 3.73 (3H, s), 4.87 (1H, m), 5.61 (1H, d, J=6.95 Hz), 6.57 (1H, s), 7.11 (6H, m), 7.32 (9H, m), 7.46 (1H, s). 13C NMR (CDCl3) 28.19, 30.34, 31.02, 50.55, 61.49, 75.62, 79.34, 119.74, 127.98, 129.59, 135.19, 137.95, 141.77, 155.19, 171.77.

Workup

  1. customThe DMF was removed
  2. additionCH2Cl2 added
  3. washThe solution was washed with dilute aqueous HCl (1M, 4X), water and brine
  4. customThe solution was dried
  5. filtrationfiltered
  6. customthe solvent removed
  7. customThe product was chromatographed (silica gel, EA/PE, Rf 0.38 EA)

Sources & evidence

ORD record
ord-8ae4b3bd33754dd2aa21ebdd47e57470
Source dataset
uspto-grants-2007_08
Patent number
US07253194B2

Reaction notes

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