Methyl iodide → HCID 60198853, compound

HRID 2279583Notes

Reaction equation

HRID 2279583 reaction equation
[CH:1]1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[N:20]([CH2:23][CH2:24][C@@H:25]([NH:33][C:34]([N:36]1[CH2:45][CH2:44][C:43]2[CH:42]=[N:41][C:40]([NH:46][CH:47]([CH3:49])[CH3:48])=[N:39][C:38]=2[CH2:37]1)=[O:35])[C:26]1[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=1)=[N+]=[N-].CI.[OH-].[K+]>C1COCC1.CO>[Cl:32][C:29]1[CH:30]=[CH:31][C:26]([C@H:25]([NH:33][C:34]([N:36]2[CH2:45][CH2:44][C:43]3[CH:42]=[N:41][C:40]([NH:46][CH:47]([CH3:49])[CH3:48])=[N:39][C:38]=3[CH2:37]2)=[O:35])[CH2:24][CH2:23][NH:20][CH3:1])=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 11776TriphenylphosphineHCID 14797Potassium HydroxideHCID 86705565HCID 86705565, compound

Product 1

HCID 60198853HCID 60198853, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of PS—PPh3 (278 mg, 2.28 mmol/g, 0.634 mmol) and THF (5 mL) was was allowed to stand for 5 min then a solution 332 (136 mg, 0.317 mmol) in THF (1 mL) was added. The suspension was stirred at RT for 4 h then MeI (0.0593 mL, 0.951 mmol) was added. The mixture was stirred at RT for 17 h, filtered through a fritted funnel and the resin washed with THF (5×10 mL) and DCM (5×10 mL). The resin was transferred to a pressure tube and suspended in MeOH (8 mL) and a solution of KOH (178 mg, 3.17 mmol) in MeOH (2 mL) was added. The mixture was heated to 65° C. for 4 h, cooled to RT, filtered and the resin washed with DCM (4×3 mL) and MeOH (2×3 mL). The filtrate and washings were combined and concentrated to a white solid. The crude product was partitioned between DCM and dilute aq. NaHCO3 and the aqueous layer extracted with EtOAc. The combined organic extracts were dried (MgSO4), filtered, and concentrated. The crude product was purified on a preparative TLC plate (0.5 mm) developed with MeOH/DCM/NH4OH (9/90/1) to afford 50 mg (38%) of I-117 as a pale yellow foam: 1H NMR (400 MHz, CDCl3) δ 8.06 (s, 1H), 7.72 (br s, 1H), 7.22-7.28 (m, 4H), 4.95 (m, 1H), 4.80 (d, 1H), 4.37 (m, 2H), 4.10 (m, 1H), 3.69 (m, 1H), 3.60 (m, 1H), 2.72 (m, 2H), 2.65 (t, 2H), 2.48 (s, 3H), 2.05 (m, 1H), 1.80 (m, 1H), 1.22 (d, 6H); LRMS (APCI pos) m/e=417.4 (M+H).

Workup

  1. stirringThe mixture was stirred at RT for 17 h
  2. filtrationfiltered through a fritted funnel
  3. washthe resin washed with THF (5×10 mL) and DCM (5×10 mL)
  4. customThe resin was transferred to a pressure tube
  5. temperatureThe mixture was heated to 65° C. for 4 h
  6. temperaturecooled to RT
  7. filtrationfiltered
  8. washthe resin washed with DCM (4×3 mL) and MeOH (2×3 mL)
  9. concentrationconcentrated to a white solid
  10. customThe crude product was partitioned between DCM and dilute aq. NaHCO3
  11. extractionthe aqueous layer extracted with EtOAc
  12. dry with materialThe combined organic extracts were dried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe crude product was purified on a preparative TLC plate (0.5 mm)
  16. customto afford 50 mg (38%) of I-117 as a pale yellow foam

Sources & evidence

ORD record
ord-49b4ff7b7a9f44f68009dbdc1d967948
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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