Acetonitrile → HCID 86661682, compound

HRID 1262132Notes

Reaction equation

HRID 1262132 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@@:27]2([OH:34])[CH2:32][CH2:31][NH:30][CH2:29][C@@H:28]2[OH:33])[CH:6]=[CH:7][C:8]=1[NH:9][C:10]1[N:15]=[CH:14][C:13]2=[CH:16][CH:17]=[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[O:25][CH3:26])[N:12]2[N:11]=1.[F:35][CH2:36][CH2:37]I.C(=O)(O)[O-].[Na+].C(#N)C>>[F:35][CH2:36][CH2:37][N:30]1[CH2:31][CH2:32][C@@:27]([C:5]2[CH:6]=[CH:7][C:8]([NH:9][C:10]3[N:15]=[CH:14][C:13]4=[CH:16][CH:17]=[C:18]([C:19]5[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=5[O:25][CH3:26])[N:12]4[N:11]=3)=[C:3]([O:2][CH3:1])[CH:4]=2)([OH:34])[C@@H:28]([OH:33])[CH2:29]1

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 69804Ethane, 1-fluoro-2-iodo-HCID 516892Sodium BicarbonateHCID 66711879HCID 66711879, compound

Product 1

HCID 86661682HCID 86661682, compoundYield 41.1%

Procedure

A mixture of (±)-(3S,4S)-4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidine-3,4-diol (42.00 mg, 0.0910 mmol), 1-fluoro-2-iodo-ethane (18.99 mg, 0.109 mmol), and sodium bicarbonate (9.174 mg, 0.109 mmol) in acetonitrile (1.000 mL, 19.15 mmol) was heated to reflux for overnight. After evaporation of volatiles under reduced pressure, the product was isolated by preparative reverse phase hplc (Gilson). Free base was obtained by catch/release work-up on acidic resin cartridge (Strata-X-C from Phenomenex) to afford (±)-(3S,4S)-1-(2-fluoro-ethyl)-4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidine-3,4-diol as a yellow foam (19 mg, 41%). 1H-NMR (CDCl3) δ 8.66 (s, 1H), 8.36 (d, J=8.4 Hz, 1H), 7.93 (d, J=7.6 Hz, 1H), 7.45 (m, 2H), 7.11 (m, 3H), 7.01 (d, J=4.6 Hz, 1H), 6.95 (d, J=8.5 Hz, 1H), 6.83 (d, J=4.6 Hz, 1H), 4.67 (m, 1H), 4.56 (m, 1H), 4.19 (dd, J=10.0; 4.8 Hz, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.00 (m, 1H), 2.85 (m, 1H), 2.75 (m, 3H), 2.55 (m, 1H), 2.44 (m, 1H), 2.07 (m, 1H), 1.90 (br s, 1H), 1.87 (m, 1H); LC/MS (ESI+): 508.0 (M+H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for overnight
  3. customAfter evaporation of volatiles under reduced pressure
  4. customthe product was isolated by preparative reverse phase hplc (Gilson)
  5. customFree base was obtained by catch/release work-up on acidic resin cartridge (Strata-X-C from Phenomenex)

Sources & evidence

ORD record
ord-966066ab019e4a37aab1f523f44ce4fd
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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