O-Phenylenediamine → Benzyl (1S)-2-[(2-aminophenyl)amino]-1-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)benzyl]-2-oxoethylcarbamate

HRID 724662Notes

Reaction equation

HRID 724662 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]2[S:27](=[O:29])(=[O:28])[NH:26][C:25](=[O:30])[CH2:24]2)=[C:19]([Br:31])[CH:18]=1)[C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.F[P-](F)(F)(F)(F)F.[N:39]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=2[N:41]=N1.C1(N)C(N)=CC=CC=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[NH2:39][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=1[NH:41][C:13](=[O:15])[C@@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]2[S:27](=[O:29])(=[O:28])[NH:26][C:25](=[O:30])[CH2:24]2)=[C:19]([Br:31])[CH:18]=1

Participants

6

Reactant 4

HCID 7243O-PhenylenediamineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 11569768(2S)-2-[(benzyloxy)carbonyl]amino-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]propanoic Acid

Product 1

HCID 11721349Benzyl (1S)-2-[(2-aminophenyl)amino]-1-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)benzyl]-2-oxoethylcarbamateYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2S)-2-[(Benzyloxy)-carbonyl]amino-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]propanoic acid (65.3 mg, 0.128 mmol) in DMF (4 mL) was treated with benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (67.8 mg, 0.153 mmol). After 5 minutes 1,2-benzenediamine (20.7 mg, 0.192 mmol) and N,N-diisopropylethylamine (111 μL, 0.638 mmol) were added and the solution stirred at rt for 2 h. Purification by preparative LCMS afforded product as a white solid (58 mg, 76%). 1H NMR (400 MHz, CD3OD): δ 7.72 (s, 1H), 7.56–7.23 (m, 10H), 6.91–6.85 (m, 1H), 5.67 (t, J=7.7 Hz, 1H), 5.09 (s, 2H), 4.50–4.47 (m, 1H), 3.46 (dd, J=16.5, 8.8 Hz, 1H), 3.34–3.24 (m, 1H), 3.26–3.08 (m, 2H); LCMS found for C26H26BrN4O6S (M+H)+: m/z=601.

Workup

  1. customPurification by preparative LCMS

Sources & evidence

ORD record
ord-d2bd779f0bca4fb58609c0bba648d9b0
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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