Acetic Anhydride → 2-Methyl-1-{4-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-1h-imidazo[4,5-c]pyridine

HRID 273047Notes

Reaction equation

HRID 273047 reaction equation
[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH2:22][NH:23][C:24]4[CH:29]=[CH:28][N:27]=[CH:26][C:25]=4[NH2:30])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:31](OC(=O)C)(=O)[CH3:32]>>[CH3:31][C:32]1[N:23]([CH2:22][C:16]2([C:13]3[CH:14]=[CH:15][C:10]([O:9][CH2:8][CH2:7][CH2:6][N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:11][CH:12]=3)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[C:24]2[CH:29]=[CH:28][N:27]=[CH:26][C:25]=2[N:30]=1

Participants

3

Reactant 2

HCID 7918Acetic AnhydrideHCID 131727198N*4*-{4-[4-(3-Pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-pyridine-3,4-diamine

Product 1

HCID 598373932-Methyl-1-{4-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-1h-imidazo[4,5-c]pyridineYield 30%

Procedure

N*4*-{4-[4-(3-Pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-pyridine-3,4-diamine (60 mg, 0.15 mmol) and acetic anhydride (˜1 mL) were stirred at reflux for 18 hours. The reaction mixture was quenched with ˜1 mL water, then basified with dilute sodium carbonate solution then extracted with DCM (2×20 mL). The organics were combined, dried over sodium sulphate, filtered and concentrated in vacuo to give a brown oil. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 to 90:10:1 by volume) to provide the title compound as a brown oil (19 mg, 30%). 1H NMR (400 MHz, CDCl3) δ 1.78-1.82 (m, 6H), 1.97-2.10 (m, 5H), 2.23 (m, 2H), 2.54 (m, 4H), 2.62 (t, 2H), 3.40 (m, 2H), 3.82 (m, 2H), 4.00 (t, 2H), 4.07 (s, 2H), 6.80-6.88 (m, 4H), 7.00 (d, 1H), 8.30 (d, 1H), 8.92 (s, 1H). LRMS ESI+ m/z 435 [MH]+.

Workup

  1. temperatureat reflux for 18 hours
  2. customThe reaction mixture was quenched with ˜1 mL water
  3. extractionthen extracted with DCM (2×20 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a brown oil
  8. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 to 90:10:1 by volume)

Sources & evidence

ORD record
ord-0766acc6b31941ba8c1e1b1a1830f3d9
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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