4-Methylmorpholine → tert-butyl 3-((2R)-2-(3-((S)-2-(benzyloxycarbonylamino)-3-(tert-butoxycarbonylamino)propanamido)-4-((dimethylamino)methyl)benzamido)-2-(2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)ethyl)-2-methoxybenzoate

HRID 1478844Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1478844
[NH2:1][C:2]1[CH:3]=[C:4]([CH:38]=[CH:39][C:40]=1[CH2:41][N:42]([CH3:44])[CH3:43])[C:5]([NH:7][C@H:8]([B:25]1[O:33][CH:32]2[C:27]([CH3:37])([CH:28]3[CH2:34][CH:30]([CH2:31]2)[C:29]3([CH3:36])[CH3:35])[O:26]1)[CH2:9][C:10]1[C:11]([O:23][CH3:24])=[C:12]([CH:20]=[CH:21][CH:22]=1)[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[O:6].[CH2:45]([O:52][C:53]([NH:55][C@@H:56]([CH2:60][NH:61][C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[C:57](O)=[O:58])=[O:54])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CN(C=O)C.O>[CH2:45]([O:52][C:53]([NH:55][C@@H:56]([CH2:60][NH:61][C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[C:57]([NH:1][C:2]1[CH:3]=[C:4]([CH:38]=[CH:39][C:40]=1[CH2:41][N:42]([CH3:43])[CH3:44])[C:5]([NH:7][C@H:8]([B:25]1[O:33][CH:32]2[C:27]([CH3:37])([CH:28]3[CH2:34][CH:30]([CH2:31]2)[C:29]3([CH3:35])[CH3:36])[O:26]1)[CH2:9][C:10]1[C:11]([O:23][CH3:24])=[C:12]([CH:20]=[CH:21][CH:22]=1)[C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])=[O:6])=[O:58])=[O:54])[C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1

Komponenten

7

Edukt 4

HCID 79724-MethylmorpholineHCID 2756240L-N-Cbz-3-N-Boc-Amino-alanineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86725255tert-butyl 3-((2R)-2-(3-amino-4-((dimethylamino)methyl)benzamido)-2-(2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)ethyl)-2-methoxybenzoate

Produkt 1

HCID 86725254tert-butyl 3-((2R)-2-(3-((S)-2-(benzyloxycarbonylamino)-3-(tert-butoxycarbonylamino)propanamido)-4-((dimethylamino)methyl)benzamido)-2-(2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)ethyl)-2-methoxybenzoate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 22350042dichloromethane N,N-dimethylformamideLösungsmittel

Versuchsvorschrift

To tert-butyl 3-((2R)-2-(3-amino-4-((dimethylamino)methyl)benzamido)-2-(2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)ethyl)-2-methoxybenzoate from step 3 in Example 18 (130 mg, 0.22 mol) and (S)-2-(benzyloxycarbonylamino)-3-(tert-butoxycarbonylamino)propanoic acid (85 mg, 0.25 mol) in DCM/DMF (4 mL, 1/1) was added NMM (1.2 eq) followed by HATU (114 mg, 0.3 mol). The reaction mixture was stirred overnight at rt. Water was added and the aqueous phase extracted with EtOAc. The organic phase was washed with IN HCl, sat. NaHCO3, brine, dried and concentrated in vacuo to afford the product (0.130 g) as a brown oil. ESI-MS m/z 926.1 (MH)+.

Aufarbeitung

  1. extractionthe aqueous phase extracted with EtOAc
  2. washThe organic phase was washed with IN HCl, sat. NaHCO3, brine
  3. customdried
  4. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-e412151a2c3940c3a9b2ec705e60a77e
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09403850B2

Notizen zur Reaktion

Wird geladen…