Water → HCID 118574239, compound

HRID 1055366Notes

Reaction equation

HRID 1055366 reaction equation
[CH3:1]CN(C(C)C)C(C)C.F[C:11](F)(F)[C:12]([OH:14])=[O:13].[NH2:17][C@H:18]1[CH2:24][O:23][C:22]2C(C(OC)=O)=[CH:26][CH:27]=[CH:28][C:21]=2[N:20]([CH2:33][C:34]2[C:43]3[C:38](=[CH:39][C:40]([Br:44])=[CH:41][CH:42]=3)[CH:37]=[CH:36][C:35]=2[O:45][CH3:46])[C:19]1=[O:47].[C:48]([O:52][C:53]([N:55]([CH3:61])[C@@H:56]([CH3:60])[C:57](O)=[O:58])=[O:54])([CH3:51])([CH3:50])[CH3:49].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>[Br:44][C:40]1[CH:39]=[C:38]2[C:43](=[CH:42][CH:41]=1)[C:34]([CH2:33][N:20]1[C:19](=[O:47])[C@@H:18]([NH:17][C:57](=[O:58])[C@@H:56]([N:55]([C:53]([O:52][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:54])[CH3:61])[CH3:60])[CH2:24][O:23][C:22]3[C:11]([C:12]([O:14][CH3:1])=[O:13])=[CH:26][CH:27]=[CH:28][C:21]1=3)=[C:35]([O:45][CH3:46])[CH:36]=[CH:37]2

Participants

9

Reactant 6

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 118574211HCID 118574211, compound

Product 1

HCID 118574239HCID 118574239, compoundYield 98.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIEA (712 mg, 972 μl, 5.51 mmol, Eq: 5.00) was added to a mixture of (S)-methyl 3-amino-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepine-9-carboxylate trifluoroacetate (660 mg, 1.1 mmol, Eq: 1.00), (S)-2-(tert-butoxycarbonyl(methyl)amino)propanoic acid (224 mg, 1.1 mmol, Eq: 1.0), HBTU (418 mg, 1.1 mmol, Eq: 1.0) and HOBT.H2O (149 mg, 1.1 mmol, Eq: 1.0) in DMF (12.5 mL) at 0° C. The mixture was warmed to RT, stirred for 1 h, diluted with EtOAc, washed with H2O, brine and dried over Na2SO4. The mixture was filtered and concentrated to afford the title compound (725 mg, 98%) as an off-white foam which was used without purification.

Workup

  1. customat 0° C
  2. washwashed with H2O, brine
  3. dry with materialdried over Na2SO4
  4. filtrationThe mixture was filtered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-c9f7e7485f1e4e48a22c7e9fee953b00
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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