Sodium cyanoborohydride → N-[[5-[[(2R)-2-[[(1,1-Dimethylethoxy)carbonyl]amino]-3-[(triphenylmethyl)thio]propyl]amino][1,1′-biphenyl]-2-yl]carbonyl]-L-methionine methyl ester

HRID 1739153Notes

Reaction equation

HRID 1739153 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:26])[C@H:5]([CH2:22][CH2:23][S:24][CH3:25])[NH:6][C:7](=[O:21])[C:8]1[CH:13]=[CH:12][C:11]([NH2:14])=[CH:10][C:9]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[C:27]([NH:34][C@H:35]([CH:57]=O)[CH2:36][S:37][C:38]([C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].C([BH3-])#N.[Na+]>CO>[CH3:2][O:3][C:4](=[O:26])[C@H:5]([CH2:22][CH2:23][S:24][CH3:25])[NH:6][C:7](=[O:21])[C:8]1[CH:13]=[CH:12][C:11]([NH:14][CH2:57][C@@H:35]([NH:34][C:27]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:28])[CH2:36][S:37][C:38]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)([C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)[C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)=[CH:10][C:9]=1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 10388929N-Boc-S-trityl-(L)-cysteinalHCID 69612387(4-Amino-2-phenylbenzoyl)methionine methyl ester hydrochloride

Product 1

HCID 18392926N-[[5-[[(2R)-2-[[(1,1-Dimethylethoxy)carbonyl]amino]-3-[(triphenylmethyl)thio]propyl]amino][1,1′-biphenyl]-2-yl]carbonyl]-L-methionine methyl esterYield 67%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of 4-amino-2-phenylbenzoyl-(S)-methionine methyl ester hydrochloride (1.27 g, 3.22 mmol) in 20 mL of methanol was added N-Boc-S-trityl-(L)-cysteinal (1.0 eq, according to 1H NMR determination of aldehyde percentage) and sodium cyanoborohydride (400 mg, 2.0 eq). The mixture was stirred for 12 hr. After the evaporation of solvents, the residue was extracted with ethyl acetate and concentrated sodium bicarbonate. After removing solvents, the residue was purified through flash column chromatography (1:1=hexane:ethyl acetate, silica) to give the product 1.67 g (yield 67%). 1H NMR (CDCl3) δ 7.65 (d, 8.6 Hz, 1H), 7.34-7.42 (m, 11H), 7.18-7.29 (m, 9H), 6.52 (dd, 2.3 and 8.1 Hz, 1H), 6.34 (d, 2.3 Hz, 1H), 5.65 (d, 7.7 Hz, 1H), 4.64 (ddd, 1H), 4.55 (d, 8.1 Hz, 1H), 4.19 (br t, 1H), 3.78 (br m, 1H), 3.64 (s, 3H), 3.09 (t, 6.1 Hz, 2H), 2.44 (m, 2H), 2.04-2.10 (m, 2H), 2.00 (s, 3H), 1.81-1.90 (m, 1H), 1.60-1.70 (m, 1H), 1.41 (s, 9H); 13C NMR (CDCl3) δ 172.0, 168.3, 155.7, 149.4, 144.3, 141.6, 141.1, 131.3, 129.5, 128.7, 128.5, 127.9, 127.7, 126.8, 122.6, 113.6, 111.3, 79.8, 67.1, 52.2, 51.7, 49.5, 47.2, 34.3, 31.6, 29.4, 28.2, 15.2.

Workup

  1. customAfter the evaporation of solvents
  2. extractionthe residue was extracted with ethyl acetate and concentrated sodium bicarbonate
  3. customAfter removing solvents
  4. customthe residue was purified through flash column chromatography (1:1=hexane:ethyl acetate, silica)

Sources & evidence

ORD record
ord-ac5840a81c124e2cbd456546ed7fcac6
Source dataset
uspto-grants-1999_10
Patent number
US05965539

Reaction notes

Loading…