Water → tert-butyl (S)-1-((S)-5-((6-((2-hydroxyethyl)(methyl)carbamoyl)-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

HRID 1055442Notes

Reaction equation

HRID 1055442 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:42])[C@@H:9]([CH3:41])[C:10]([NH:12][C@H:13]1[CH2:19][O:18][C:17]2[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=2[N:15]([CH2:24][C:25]2[C:34]([O:35][CH3:36])=[CH:33][CH:32]=[C:31]3[C:26]=2[CH:27]=[CH:28][C:29]([C:37]([OH:39])=O)=[CH:30]3)[C:14]1=[O:40])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:43][NH:44][CH2:45][CH2:46][OH:47].C1C=CC2N(O)N=NC=2C=1.O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[OH:47][CH2:46][CH2:45][N:44]([CH3:43])[C:37]([C:29]1[CH:30]=[C:31]2[C:26](=[CH:27][CH:28]=1)[C:25]([CH2:24][N:15]1[C:14](=[O:40])[C@@H:13]([NH:12][C:10](=[O:11])[C@@H:9]([N:8]([CH3:42])[C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH3:41])[CH2:19][O:18][C:17]3[CH:20]=[CH:21][CH:22]=[CH:23][C:16]1=3)=[C:34]([O:35][CH3:36])[CH:33]=[CH:32]2)=[O:39]

Participants

9

Reactant 6

HCID 962WaterHCID 80162-(Methylamino)ethanolHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1185741935-(((S)-3-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-4-oxo-3,4-dihydrobenzo[b][1,4]oxazepin-5(2H)-yl)methyl)-6-methoxy-2-naphthoic acid

Product 1

HCID 131736359tert-butyl (S)-1-((S)-5-((6-((2-hydroxyethyl)(methyl)carbamoyl)-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamateYield 85.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-(((S)-3-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-4-oxo-3,4-dihydrobenzo[b][1,4]oxazepin-5(2H)-yl)methyl)-6-methoxy-2-naphthoic acid (100 mg, 173 μmol, Eq: 1.00), 2-(methylamino)ethanol (26.0 mg, 27.8 μl, 346 μmol, Eq: 2.00), HOBT.H2O (31.8 mg, 208 μmol, Eq: 1.20), HBTU (78.8 mg, 208 μmol, Eq: 1.2), DIEA (67.1 mg, 90.5 μl, 519 μmol, Eq: 3.00) in DMF was stirred at 0° C. for 2 h. The mixture was diluted with EtOAc, washed with water, brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography to afford tert-butyl (S)-1-((S)-5-((6-((2-hydroxyethyl)(methyl)carbamoyl)-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (94 mg, 85% yield) as an oil.

Workup

  1. washwashed with water, brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-df8b2e2309c54d5ba96ba39eaa94fcb4
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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