Acetic Acid → (S)-tert-Butyl 7-(((3S,5S)-1-(tert-butoxycarbonyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)amino)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 339242Notes

Reaction equation

HRID 339242 reaction equation
O=[C:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14](=[O:26])[NH:15][C@H:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:19][CH2:18][CH2:17]2)[CH2:3]1.[NH2:27][C:28]1[CH:37]=[C:36]2[C:31]([CH2:32][C@@H:33]([C:45](=[O:57])[NH:46][C@H:47]3[C:56]4[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=4)[CH2:50][CH2:49][CH2:48]3)[N:34]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:35]2)=[CH:30][CH:29]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].Cl>ClCCCl.CCOC(C)=O>[C:10]([O:9][C:7]([N:5]1[C@H:4]([C:14](=[O:26])[NH:15][C@H:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:19][CH2:18][CH2:17]2)[CH2:3][C@H:2]([NH:27][C:28]2[CH:37]=[C:36]3[C:31]([CH2:32][C@@H:33]([C:45](=[O:57])[NH:46][C@H:47]4[C:56]5[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=5)[CH2:50][CH2:49][CH2:48]4)[N:34]([C:38]([O:40][C:41]([CH3:42])([CH3:43])[CH3:44])=[O:39])[CH2:35]3)=[CH:30][CH:29]=2)[CH2:6]1)=[O:8])([CH3:13])([CH3:11])[CH3:12]

Participants

8

Reactant 5

HCID 176Acetic Acid2×HCID 313Hydrochloric AcidHCID 5049666Sodium triacetoxyborohydride2×HCID 86705874(S)-tert-Butyl 4-oxo-2-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidine-1-carboxylateHCID 86705875(S)-tert-Butyl 7-amino-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 86705877(S)-tert-Butyl 7-(((3S,5S)-1-(tert-butoxycarbonyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)amino)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 98.8%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-tert-butyl 4-oxo-2-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidine-1-carboxylate (73 mg, 0.20 mmol) in DCE (2.0 mL) was added (S)-tert-butyl 7-amino-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (86 mg, 0.20 mmol) and AcOH (12 μL, 0.20 mmol). Na(OAc)3BH (78 mg, 0.37 mmol) was then added, and the resulting reaction mixture was stirred at room temperature for 4 h. Additional AcOH (12 μL, 0.20 mmol) and Na(OAc)3BH (78 mg, 0.37 mmol) were added, and stirring was continued overnight at room temperature. The reaction mixture was poured into a separatory funnel containing 1N HCl and EtOAc. The aqueous layer was extracted with EtOAc (3×). The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to give the title compound (151 mg, 97%) as a colorless oil. MS (ESI+) m/z 764.5 (M+H)+.

Workup

  1. customthe resulting reaction mixture
  2. stirringstirring
  3. waitwas continued overnight at room temperature
  4. additionThe reaction mixture was poured into a separatory funnel
  5. extractionThe aqueous layer was extracted with EtOAc (3×)
  6. washThe combined organics were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a711ec0a857546eca32caa6d6bb2e16c
Source dataset
uspto-grants-2014_11
Patent number
US08889712B2

Reaction notes

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