Diisopropylethylamine → (1S,3S,4R)-tert-butyl 3-(1-amino-6-bromonaphthalen-2-ylcarbamoyl)-2-azabicyclo[2.2.1]heptane-2-carboxylate

HRID 1751613Notes

Reaction equation

HRID 1751613 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH2:13])[C:8]=2[NH2:12])[CH:3]=1.[C:14]([O:18][C:19]([N:21]1[C@H:26]([C:27](O)=[O:28])[C@H:25]2[CH2:30][C@@H:22]1[CH2:23][CH2:24]2)=[O:20])([CH3:17])([CH3:16])[CH3:15].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>[NH2:12][C:8]1[C:9]2[C:4](=[CH:3][C:2]([Br:1])=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[NH:13][C:27]([C@@H:26]1[C@H:25]2[CH2:30][C@H:22]([CH2:23][CH2:24]2)[N:21]1[C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:20])=[O:28]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 220970716-Bromonaphthalene-1,2-diamineHCID 69134534rac-(1R,3R,4S)-2-[(tert-butoxy)carbonyl]-2-azabicyclo[2.2.1]heptane-3-carboxylic acid

Product 1

HCID 86708790(1S,3S,4R)-tert-butyl 3-(1-amino-6-bromonaphthalen-2-ylcarbamoyl)-2-azabicyclo[2.2.1]heptane-2-carboxylateYield 95.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-bromonaphthalene-1,2-diamine (1.08 g, 4.56 mmol), and (1S,3S,4R)-2-(tert-butoxycarbonyl)-2-azabicyclo[2.2.1]heptane-3-carboxylic acid (1.10 g, 4.56 mmol) and HATU (2.08 g, 5.47 mmol) in methylene chloride (45 mL) was added DIPEA (3.98 mL, 22.79 mmol). The mixture was stirred at room temperature for two hours. Upon completion, the reaction was concentrated in vacuo, diluted with ethyl acetate and washed with water. The aqueous layer was back extracted with ethyl acetate twice. The combined organic layers were washed with brine, concentrated, and purified by normal phase chromatography (30-80% ethyl acetate (5% MeOH) in hexanes) to give (1S,3S,4R)-tert-butyl 3-(1-amino-6-bromonaphthalen-2-ylcarbamoyl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (2.01 g, 95%). LCMS-ESI+: calc'd for C22H26BrN3O3: 459.12 (M+); Found: 460.9 (M+H+).

Workup

  1. concentrationUpon completion, the reaction was concentrated in vacuo
  2. additiondiluted with ethyl acetate
  3. washwashed with water
  4. extractionThe aqueous layer was back extracted with ethyl acetate twice
  5. washThe combined organic layers were washed with brine
  6. concentrationconcentrated
  7. custompurified by normal phase chromatography (30-80% ethyl acetate (5% MeOH) in hexanes)

Sources & evidence

ORD record
ord-7fd4bacfec5141c3a8a34c869445b631
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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