Water → HCID 131736357, compound

HRID 1055433Notes

Reaction equation

HRID 1055433 reaction equation
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.[NH2:36][CH:37]1[C:43]2([CH2:48][CH2:47][O:46][CH2:45][CH2:44]2)[O:42][C:41]2[CH:49]=[CH:50][CH:51]=[CH:52][C:40]=2[NH:39][C:38]1=[O:53].[NH:54]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[C@H:55]([C:57](O)=[O:58])[CH3:56]>CN(C=O)C.CCOC(C)=O>[O:58]=[C:57]([NH:36][CH:37]1[C:43]2([CH2:44][CH2:45][O:46][CH2:47][CH2:48]2)[O:42][C:41]2[CH:49]=[CH:50][CH:51]=[CH:52][C:40]=2[NH:39][C:38]1=[O:53])[C@@H:55]([NH:54][C:60](=[O:61])[O:62][C:63]([CH3:66])([CH3:65])[CH3:64])[CH3:56]

Participants

8

Reactant 5

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 85082Tert-butoxycarbonylalanineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 72712774HCID 72712774, compound

Product 1

HCID 131736357HCID 131736357, compoundYield 91%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of HBTU (550 mg, 1.45 mmol, Eq: 1.2) and HOBT.H2O (222 mg, 1.45 mmol, Eq: 1.2) in DMF (8 mL) were added to a solution of 3-amino-2′,3′,5′,6′-tetrahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4′-pyran]-4(5H)-one (0.3 g, 1.21 mmol, Eq: 1.00), BOC-Ala-OH (229 mg, 1.21 mmol, Eq: 1.00) and TEA (367 mg, 505 μl, 3.62 mmol, Eq: 3) in DMF (8 mL). After 2 d, the mixture was poured into EtOAc, washed with 1:1 sat NaHCO3/sat NaCl, brine, dried over Na2SO4 and concentrated. The residue was purified by flash chromatography to afford tert-butyl (2S)-1-oxo-1-(4-oxo-2′,3′,4,5,5′,6′-hexahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4′-pyran]-3-ylamino)propan-2-ylcarbamate (0.46 g, 91%) as a white foam. MS m/z 420.0 (MH+)

Workup

  1. washwashed with 1:1
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-bfaa9236fd3448e19e8de205e383e864
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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