Trimethyl orthoformate → 3-({4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2h-pyran-4-yl}methyl)-3h-imidazo[4,5-b]pyridine

HRID 273050Notes

Reaction equation

HRID 273050 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[C:29]([NH2:30])=[CH:28][CH:27]=[CH:26][N:25]=4)[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.[CH3:31]OC(OC)OC>C(O)=O>[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][N:23]4[C:24]5=[N:25][CH:26]=[CH:27][CH:28]=[C:29]5[N:30]=[CH:31]4)[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 9005Trimethyl orthoformateHCID 131727199N*2*-{4-[4-(3-Pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-pyridine-2,3-diamine

Product 1

HCID 598374423-({4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2h-pyran-4-yl}methyl)-3h-imidazo[4,5-b]pyridineYield 71%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

N*2*-{4-[4-(3-Pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-pyridine-2,3-diamine (350 mg, 0.85 mmol), trimethylorthoformate (5 mL) and formic acid (0.5 mL) were stirred at 40° C. for 3 hours. The reaction mixture was concentrated in vacuo and the residue partitioned between saturated NaHCO3 solution (40 mL) and DCM (2×40 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 (97:3:0.3 to 93:7:0.7 by volume) to provide the title compound as a brown oil (255 mg, 71%). 1H NMR (400 MHz, CDCl3) δ 1.78-1.82 (m, 4H), 1.99-2.10 (m, 6H), 2.57 (m, 4H), 2.64 (t, 2H), 3.56 (m, 2H), 3.92 (m, 2H), 4.03 (t, 2H), 4.40 (s, 2H), 6.82 (s, 1H), 6.90 (d, 2H), 7.02 (d, 2H), 7.20 (m, 1H), 7.99 (d, 1H), 8.38 (d, 1H). HRMS ESI+ m/z 421.2586 [MH]+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue partitioned between saturated NaHCO3 solution (40 mL) and DCM (2×40 mL)
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a brown oil
  7. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (97:3:0.3 to 93:7:0.7 by volume)

Sources & evidence

ORD record
ord-486d4360df3a4479a278fa6b88eb4f22
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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