4-Methylmorpholine → methyl N-[(2S,3S)-1-[[(2S,3S)-3-hydroxy-4-[[[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-[[4-(1,3-thiazol-2-yl)phenyl]methyl]amino]-1-phenylbutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamate

HRID 380211Notes

Reaction equation

HRID 380211 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[CH:11]=[CH:10][C:9]([CH2:12][N:13]([NH2:38])[CH2:14][C@H:15]([OH:37])[C@@H:16]([NH:24][C:25](=[O:36])[C@H:26]([C@H:32]([CH2:34][CH3:35])[CH3:33])[NH:27][C:28]([O:30][CH3:31])=[O:29])[CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:8][CH:7]=1.CN1CCOCC1.[CH3:46][O:47][C:48]([NH:50][C@H:51]([C:55](O)=[O:56])[CH:52]([CH3:54])[CH3:53])=[O:49].[B-](F)(F)(F)F.CN(C(ON1C(=O)C=CC=C1)=[N+](C)C)C>CN(C=O)C.C(Cl)Cl.C1COCC1>[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[CH:7]=[CH:8][C:9]([CH2:12][N:13]([NH:38][C:55](=[O:56])[C@H:51]([CH:52]([CH3:53])[CH3:54])[NH:50][C:48]([O:47][CH3:46])=[O:49])[CH2:14][C@H:15]([OH:37])[C@@H:16]([NH:24][C:25](=[O:36])[C@H:26]([C@H:32]([CH2:34][CH3:35])[CH3:33])[NH:27][C:28]([O:30][CH3:31])=[O:29])[CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:10][CH:11]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733204O-(2-Oxo-1(2H)-pyridyl)-N,N,N',N'-tetramethyluronium TetrafluoroborateHCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 665781701-[4-(Thiazol-2-yl)-phenyl]-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-iso-leucyl)amino-6-phenyl-2-azahexane

Product 1

HCID 467968methyl N-[(2S,3S)-1-[[(2S,3S)-3-hydroxy-4-[[[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]amino]-[[4-(1,3-thiazol-2-yl)phenyl]methyl]amino]-1-phenylbutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

Under an argon atmosphere, 321 mg (0.60 mmol) of 1-[4-(thiazol-2-yl)-phenyl]-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-iso-leucyl)amino-6-phenyl-2-azahexane (Example 21b) and 182 mg (1.8 mmol) of NMM in 5.8 ml of DMF are added to 126 mg (0.72 mmol) of N-methoxycarbonyl-(L)-valine and 178 mg (0.60 mmol) of TPTU in 3 ml of DMF; the mixture is stirred at room temperature for 15 hours and worked up analogously to Example 3. TLC: Rf=0.15 (methylene chloride/THF 4:1); HPLC20-100: tRet=14.5; FAB MS (M+H)+=697.

Sources & evidence

ORD record
ord-11261abfa2024092a55d505d66b66827
Source dataset
uspto-grants-2001_10
Patent number
US06300519B1

Reaction notes

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