Azidotrimethylsilane → HCID 178491865, compound

HRID 1614874Notes

Reaction equation

HRID 1614874 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][C@H:11]2[CH2:15][CH2:14][C@@H:13]([C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=3)[CH2:12]2)[CH3:9])=[CH:4][C:3]=1[O:24][CH3:25].C[Si]([N:30]=[N+:31]=[N-:32])(C)C>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][C@H:11]2[CH2:15][CH2:14][C@@H:13]([C:16]3[CH:17]=[CH:18][C:19]([C:20]4[NH:32][N:31]=[N:30][N:21]=4)=[CH:22][CH:23]=3)[CH2:12]2)[CH3:9])=[CH:4][C:3]=1[O:24][CH3:25]

Participants

4

Reactant 2

HCID 78378AzidotrimethylsilaneHCID 687501784-[(1R,3S)-3-[[(1R)-1-(4-fluoro-3-methoxy-phenyl)ethyl]amino]cyclopentyl]benzonitrile

Product 1

HCID 178491865HCID 178491865, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
118 °C

Procedure

4-[(1R,3S)-3-[[(1R)-1-(4-fluoro-3-methoxy-phenyl)ethyl]amino]cyclopentyl]benzonitrile (5.1 g, 14.4 mmol) in toluene (160 ml) was treated with trimethylsilylazide (9.5 ml, 72 mmol, dropwise addition) followed by SnBu2O (717 mg, 2.88 mmol). The reaction mixture was stirred at 118° C. overnight. The precipitate was filtered off, and the filtrate was evaporated and purified by flash chromatography (gradient of 0-10%, MeOH in DCM containing 2% NEt3). The product thus obtained was precipitated from EtOH, redissolved in DCM and extracted with aqueous HCl (pH 1). The aqueous phase was neutralized to pH 5-6 with NaOH aq. (1M), and the resulting precipitate was filtered off and dried to afford the title compound. 1H NMR (300 MHz, DMSO) δ 7.89 (d, J=8.2 Hz, 2H), 7.39 (dd, J=8.3, 1.8 Hz, 1H), 7.33-7.23 (m, 3H), 7.14-7.03 (m, 1H), 4.38 (q, J=6.5 Hz, 1H), 3.86 (s, 3H), 3.45-3.32 (m, 1H), 3.09-2.95 (m, 1H), 2.38-2.25 (m, 1H), 2.10-1.64 (m, 5H), 1.56 (d, J=6.7 Hz, 3H).

Workup

  1. addition9.5 ml, 72 mmol, dropwise addition)
  2. filtrationThe precipitate was filtered off
  3. customthe filtrate was evaporated
  4. custompurified by flash chromatography (gradient of 0-10%, MeOH in DCM containing 2% NEt3)
  5. customThe product thus obtained
  6. customwas precipitated from EtOH
  7. dissolutionredissolved in DCM
  8. extractionextracted with aqueous HCl (pH 1)
  9. filtrationthe resulting precipitate was filtered off
  10. customdried

Sources & evidence

ORD record
ord-3fd69901f4b94502a1650e0fd362ad83
Source dataset
uspto-grants-2014_07
Patent number
US08765676B2

Reaction notes

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