N-((1,1-dimethylethoxy)carbonyl)-beta-alanine → methyl(7R)-7-[[N-(tert-butoxycarbonyl)-beta-alanyl](methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

HRID 421937Notes

Reaction equation

HRID 421937 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:28]([O:30][CH3:31])=[O:29])=[CH:12][C:13]=3[N:14]3[C:21]=2[C:20]2[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=2[O:18][CH2:17][C@H:16]([NH:26][CH3:27])[CH2:15]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:32]([O:36][C:37]([NH:39][CH2:40][CH2:41][C:42]([OH:44])=O)=[O:38])([CH3:35])([CH3:34])[CH3:33].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.CCOC(C)=O>[C:32]([O:36][C:37]([NH:39][CH2:40][CH2:41][C:42]([N:26]([CH3:27])[C@@H:16]1[CH2:15][N:14]2[C:13]3[CH:12]=[C:11]([C:28]([O:30][CH3:31])=[O:29])[CH:10]=[CH:9][C:8]=3[C:7]([CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[C:21]2[C:20]2[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=2[O:18][CH2:17]1)=[O:44])=[O:38])([CH3:33])([CH3:34])[CH3:35]

Participants

7

Reactant 4

HCID 76809N-((1,1-dimethylethoxy)carbonyl)-beta-alanineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66674181methyl(7R)-14-cyclohexyl-7-(methylamino)-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

Product 1

HCID 66674302methyl(7R)-7-[[N-(tert-butoxycarbonyl)-beta-alanyl](methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl(7R)-14-cyclohexyl-7-(methylamino)-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate (prepared as described in Example 1, Step 5) and N-(tert-butoxycarbonyl)-β-alanine (1.2 eq) in DCM (0.15 M) was treated with HATU (1.3 eq.) and DIPEA (3 eq.) and the resulting mixture was stirred for 90 min at RT. The reaction was diluted with EtOAc and the combined organic layers were washed with 1N HCl (aq), sat aq NaHCO3 then brine, before being dried (Na2SO4), filtered and concentrated in vacuo. The product was used directly in the next step without further purification. (ES+) m/z 590 (M+H)+.

Workup

  1. washthe combined organic layers were washed with 1N HCl (aq)
  2. dry with materialbrine, before being dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe product was used directly in the next step without further purification

Sources & evidence

ORD record
ord-e6154159237744ed915756e12a14e44f
Source dataset
uspto-grants-2012_01
Patent number
US08101595B2

Reaction notes

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