Diisopropylethylamine → HCID 178452531, compound

HRID 1527364Notes

Reaction equation

HRID 1527364 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:13]([C:14]([OH:16])=O)[CH2:12][C@@H:11]2[C@H:9]1[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[Br:19][C:20]1[CH:21]=[C:22]([NH2:31])[CH:23]=[C:24]([C:26]2[NH:30][N:29]=[N:28][N:27]=2)[CH:25]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[C@H:13]([C:14](=[O:16])[NH:31][C:22]2[CH:23]=[C:24]([C:26]3[NH:30][N:29]=[N:28][N:27]=3)[CH:25]=[C:20]([Br:19])[CH:21]=2)[CH2:12][C@@H:11]2[C@H:9]1[CH2:10]2)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11020613(1R,3S,5R)-2-(tert-Butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acidHCID 178478649HCID 178478649, compound

Product 1

HCID 178452531HCID 178452531, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-tert-butyl ester (250 mg, 1.1 mmol) in CH2Cl2 (6 mL) was added 3-bromo-5-(1H-tetrazol-5-yl)-phenylamine dihydrochloride (prepared as described in Part C, 365 mg, 1.32 mmol), HBTU (626 mg, 1.65 mmol) and DIPEA (0.576 ml, 3.3 mmol). The reaction mixture was stirred at RT overnight. The reaction mixture was diluted with CH2Cl2 and successively washed with 1M aqueous HCl solution (30 mL) and a saturated aqueous NaHCO3 solution. The organic phase was dried (phase separator) and evaporated under vacuum. The crude mixture was purified by preparative HPLC (C18 Nucleosil 100-10, flow: 40 ml/min, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA). After combination of the purified fractions, CH3CN was removed under vacuum and lyophilization gave the desired compound. MS (LC/MS): 447.1 [M−H]−; tR (HPLC conditions k): 4.62 min.

Workup

  1. washsuccessively washed with 1M aqueous HCl solution (30 mL)
  2. customThe organic phase was dried (phase separator)
  3. customevaporated under vacuum
  4. customThe crude mixture was purified by preparative HPLC (C18 Nucleosil 100-10, flow: 40 ml/min, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA)
  5. customAfter combination of the purified fractions, CH3CN was removed under vacuum and lyophilization

Sources & evidence

ORD record
ord-06272db0913c4714abc96c7a8da096d3
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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