Water → HCID 90036988, compound

HRID 1055452Notes

Reaction equation

HRID 1055452 reaction equation
CCN(C(C)C)C(C)C.[Br:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C:17]([CH2:21][N:22]1[C:28](=[O:29])[C@@H:27]([NH:30][C:31](=[O:43])[C@@H:32]([N:34]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH3:35])[CH3:33])[CH2:26][O:25][C:24]3[C:44]([C:48](O)=[O:49])=[CH:45][CH:46]=[CH:47][C:23]1=3)=[C:16]([O:51][CH3:52])[CH:15]=[CH:14]2.Cl.[NH2:54][CH2:55][CH2:56][C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.O>CN(C=O)C.CCOC(C)=O>[C:60]([O:59][C:57](=[O:58])[CH2:56][CH2:55][NH:54][C:48]([C:44]1[C:24]2[O:25][CH2:26][C@H:27]([NH:30][C:31](=[O:43])[C@@H:32]([N:34]([C:36]([O:38][C:39]([CH3:41])([CH3:42])[CH3:40])=[O:37])[CH3:35])[CH3:33])[C:28](=[O:29])[N:22]([CH2:21][C:17]3[C:18]4[C:13](=[CH:12][C:11]([Br:10])=[CH:20][CH:19]=4)[CH:14]=[CH:15][C:16]=3[O:51][CH3:52])[C:23]=2[CH:47]=[CH:46][CH:45]=1)=[O:49])([CH3:63])([CH3:62])[CH3:61]

Participants

9

Reactant 6

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 16218890Tert-butyl 3-aminopropanoate hydrochlorideHCID 118574037HCID 118574037, compound

Product 1

HCID 90036988HCID 90036988, compoundYield 69.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIEA (177 mg, 242 μl, 1.37 mmol, Eq: 5.00) was added to a mixture of (S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-3-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepine-9-carboxylic acid (180 mg, 274 μmol, Eq: 1.00), tert-butyl 3-aminopropanoate hydrochloride (49.8 mg, 274 μmol, Eq: 1.00), HBTU (104 mg, 274 μmol, Eq: 1.0) and HOBT.H2O (37.0 mg, 274 μmol, Eq: 1.0) in DMF (3.41 mL) at 0° C. and the mixture was warmed to RT. After 45 min. the mixture was diluted with EtOAc, washed with H2O, brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel chromatography to afford 3-({(S)-9-(6-bromo-2-methoxy-naphthalen-1-ylmethyl)-7-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocycloheptene-4-carbonyl}-amino)-propionic acid tert-butyl ester (150 mg, 69%) as an off-white foam.

Workup

  1. washwashed with H2O, brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-21fdb5c4609b4c4885e9fc1d7aeaf0c8
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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