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 2208577Notes

Reaction equation

HRID 2208577 reaction equation
[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

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

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 1N 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)+.

Workup

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

Sources & evidence

ORD record
ord-d2262986898c46aeb902329350766c51
Source dataset
uspto-grants-2016_06
Patent number
US09376454B2

Reaction notes

Loading…