Triphenylphosphine → N-[(1R,2R)-2-azido-2,3-dihydro-1H-inden-1-yl]-3,6-dicyclopropyl-5-(2,4-dichlorophenyl)pyrazin-2-amine

HRID 1612353Notes

Reaction equation

HRID 1612353 reaction equation
[CH:1]1([C:4]2[C:5]([NH:21][C@@H:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH2:24][C@@H:23]3O)=[N:6][C:7]([CH:18]3[CH2:20][CH2:19]3)=[C:8]([C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=3[Cl:17])[N:9]=2)[CH2:3][CH2:2]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[NH:51]=[N+:52]=[N-:53].CCOC(/N=N/C(OCC)=O)=O>C1(C)C=CC=CC=1.C1COCC1>[N:51]([C@@H:23]1[CH2:24][C:25]2[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@H:22]1[NH:21][C:5]1[C:4]([CH:1]2[CH2:3][CH2:2]2)=[N:9][C:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=2[Cl:17])=[C:7]([CH:18]2[CH2:19][CH2:20]2)[N:6]=1)=[N+:52]=[N-:53]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 24530Hydrazoic acidHCID 5462977Diethyl azodicarboxylateHCID 58583473(1R,2S)-1-{[3,6-dicyclopropyl-5-(2,4-dichlorophenyl)pyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol

Product 1

HCID 58583346N-[(1R,2R)-2-azido-2,3-dihydro-1H-inden-1-yl]-3,6-dicyclopropyl-5-(2,4-dichlorophenyl)pyrazin-2-amineYield 98.6%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (1R,2S)-1-{[3,6-dicyclopropyl-5-(2,4-dichlorophenyl)pyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol (0.76 g, 1.7 mmol) in toluene (10 mL) and THF (10 mL) was added PPh3 (1.14 g, 4.57 mmol). The solution was cooled to 0° C. and HN3 (5.6 mL, 6.38 mmol) and a solution of diethylazodicarboxylate (0.69 mL, 4.37 mmol) in toluene (10 mL) were added. The reaction was stirred at rt overnight. The precipitates were removed by filtration and the filtrate was concentrated. Dissolve residue in 1 N HCl and EtOAc. Extract with EtOAc (3×30 mL). The aqueous phase was neutralized with sat. aq. NaHCO3 to pH 7.5 followed by a small amount of 6 N NaOH to pH 9. The aqueous phase was extracted with CH2Cl2 (3×30 mL). The combined organic extracts were dried over MgSO4, filtered and concentrated. Purify by biotage MPLC (90 g column, 29-39% ethyl acetate/hexanes) to afford 0.8 g (78%) of N-[(1R,2R)-2-azido-2,3-dihydro-1H-inden-1-yl]-3,6-dicyclopropyl-5-(2,4-dichlorophenyl)pyrazin-2-amine as a solid: 1H NMR (CDCl3) δ 0.74-1.10, 1.63-1.71, 2.97-3.03, 3.36-3.42, 4.09-4.13, 4.26-4.29, 5.05, 5.57, 7.25-7.53; MS (ESI+) for C25H22Cl2N6 m/z 477 (M+H)+.

Workup

  1. customThe precipitates were removed by filtration
  2. concentrationthe filtrate was concentrated
  3. extractionExtract with EtOAc (3×30 mL)
  4. extractionThe aqueous phase was extracted with CH2Cl2 (3×30 mL)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurify by biotage MPLC (90 g column, 29-39% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-073dd8e0411741808149060e4038216f
Source dataset
uspto-grants-2006_01
Patent number
US06992087B2

Reaction notes

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