(Bis(2-methoxyethyl)amino)sulfur trifluoride → 3-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-fluoroazetidine-1-carboxylic acid tert-butyl ester

HRID 1923374Notes

Reaction equation

HRID 1923374 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([C:13]2[N:14]([CH3:39])[C:15]3[C:20]([N:21]=2)=[C:19]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[N:18]=[C:17]([N:28]2[C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=4[N:30]=[C:29]2[CH2:37][CH3:38])[N:16]=3)(O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].COCCN(S(F)(F)[F:50])CCOC>C1COCC1>[CH2:37]([C:29]1[N:28]([C:17]2[N:16]=[C:15]3[C:20]([N:21]=[C:13]([C:10]4([F:50])[CH2:11][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9]4)[N:14]3[CH3:39])=[C:19]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[N:18]=2)[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[N:30]=1)[CH3:38]

Participants

4

Reactant 2

HCID 2734690(Bis(2-methoxyethyl)amino)sulfur trifluorideHCID 596058743-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-hydroxy-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 596054193-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-fluoroazetidine-1-carboxylic acid tert-butyl esterYield 79.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of 3-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-hydroxy-azetidine-1-carboxylic acid tert-butyl ester (300 mg, 0.56 mmol) in THF (2 mL) at 5° C. was added a solution of bis-(2-methoxyethyl)aminosulfur trifluoride (275 μL, 0.62 mmol, 50% solution in THF) in THF (3 mL). The resulting mixture was allowed to stir at 5° C. for 15 min then warmed to r.t. and stirred for a further 15 min. The reaction mixture was partitioned between sat. aq. NaHCO3 and DCM, the organic phase dried (phase separator) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, EtOAc:cyclohexane, 35-85%) affording 828 as a pale yellow solid (238 mg, 79%). LCMS (method I): RT 4.65 min, [M+H]+ 537.4. 1H NMR (DMSO, 400 MHz): δ 8.05-8.04 (1 H, m), 7.64-7.64 (1 H, m), 7.26-7.25 (2 H, m), 4.77 (2 H, dd, J=20.08, 10.62 Hz), 4.60-4.10 (4 H, brd s), 4.48 (2 H, dd, J=21.54, 10.50 Hz), 3.79 (4 H, t, J=4.55 Hz), 3.76 (3 H, d, J=1.32 Hz), 3.28-3.27 (2 H, m), 1.42 (9 H, s), 1.34 (3 H, t, J=7.46 Hz)

Workup

  1. temperaturethen warmed to r.t.
  2. stirringstirred for a further 15 min
  3. customThe reaction mixture was partitioned between sat. aq. NaHCO3 and DCM
  4. customthe organic phase dried (phase separator)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (Si-PCC, EtOAc:cyclohexane, 35-85%)

Sources & evidence

ORD record
ord-0513d1ce719c4840bfdaa3187c76c037
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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