Benzhydrylamine → HCID 178427601, compound

HRID 622624Notes

Reaction equation

HRID 622624 reaction equation
[CH:1]([NH2:14])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([NH:25][C:26]([NH2:43])=[N:27][CH2:28][CH2:29][CH2:30][C@H:31]([NH:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[C:32]([OH:34])=[O:33])(=[O:24])=[O:23])=[CH:18][CH:17]=1.C1CCC(N=C=NC2CCCCC2)CC1.C(N(C(C)C)CC)(C)C.N[C@H](C(O)=O)CCCNC(=N)N.C1C=NC(C2C=C(Br)C=CC=2F)=C(F)C=1>CN(C=O)C.C(Cl)Cl>[NH:35]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[C@H:31]([C:32]([OH:34])=[O:33])[CH2:30][CH2:29][CH2:28][NH:27][C:26](=[NH:43])[NH:25][S:22]([C:19]1[CH:20]=[CH:21][C:16]([CH3:15])=[CH:17][CH:18]=1)(=[O:24])=[O:23].[CH:1]([NH2:14])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 6

HCID 7036BenzhydrylamineHCID 10868DicyclohexylcarbodiimideHCID 81531DiisopropylethylamineHCID 83767L-Ornithine, N2-[(1,1-dimethylethoxy)carbonyl]-N5-[imino[[(4-methylphenyl)sulfonyl]amino]methyl]-HCID 115435872-(5-Bromo-2-fluorophenyl)-3-fluoropyridineHCID 178418600HCID 178418600, compound

Product 1

HCID 178427601HCID 178427601, compound

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

Benzhydrylamine-resin (40.44g 0.5 mmol/g, 20.22 mmol) was coupled with Boc Arg (Tos)-OH(34.6g, 80.7 mmol) in 25% DMF-CH2Cl2 with DCC (16.78g, 81.4 mmol) for 2h followed by the addition of 1% diisopropylethylamine and reacted for 0.5 h longer. The resultant Boc-Arg (Tos)-BHA-resin was washed with CH2Cl2 (3×250 mL), MeOH(3×250 mL), CH2Cl2 (3×250 mL) and dried. The couplings and washing procedures were repeated and an aliquot was hydrolyzed (1 mL of 6M propionic acid/HCl at 130° for 2 h). Amino acid analysis showed a substitution of 0.35 mmol of Arg per gram of resin. The remaining amino groups were acetylated with AC2 0-Pyridine. Yield 48.88g (Boc-Arg(Tos)-BHA-resin, 4).

Workup

  1. customreacted for 0.5 h longer
  2. washThe resultant Boc-Arg (Tos)-BHA-resin was washed with CH2Cl2 (3×250 mL), MeOH(3×250 mL), CH2Cl2 (3×250 mL)
  3. customdried
  4. washThe couplings and washing procedures
  5. custom(1 mL of 6M propionic acid/HCl at 130° for 2 h)

Sources & evidence

ORD record
ord-34c6a4b879324a1db640e6207140d708
Source dataset
uspto-grants-1988_09
Patent number
US04772547

Reaction notes

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