1,2-Dichloroethane → N-[2-(Hydroxymethyl)-3-pyridinyl]-2-[(phenylmethyl)oxy]-5-(4-pyridinyl)benzamide

HRID 1623796Notes

Reaction equation

HRID 1623796 reaction equation
[NH2:1][C:2]1[C:3]([CH2:8][OH:9])=[N:4][CH:5]=[CH:6][CH:7]=1.[C:10]1([CH2:16][O:17][C:18]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=3)=[CH:23][C:19]=2[C:20](O)=[O:21])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C)C=O.O>[OH:9][CH2:8][C:3]1[C:2]([NH:1][C:20](=[O:21])[C:19]2[CH:23]=[C:24]([C:27]3[CH:28]=[CH:29][N:30]=[CH:31][CH:32]=3)[CH:25]=[CH:26][C:18]=2[O:17][CH2:16][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 15645802(3-Aminopyridin-2-yl)methanolHCID 669904822-(Benzyloxy)-5-(pyridin-4-yl)benzoic acid

Product 1

HCID 69936751N-[2-(Hydroxymethyl)-3-pyridinyl]-2-[(phenylmethyl)oxy]-5-(4-pyridinyl)benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
15 °C

Procedure

Neat (3-aminopyridin-2-yl)methanol (may be prepared as described in Description 80; 68 mg, 0.55 mmol) was added in one charge to a stirred suspension of 2-[(phenylmethyl)oxy]-5-(4-pyridinyl)benzoic acid (may be prepared as described in Description 79; 120 mg, 0.393 mmol), EDC (151 mg, 0.786 mmol), HOBT (120 mg, 0.79 mmol) and triethylamine (0.11 ml, 0.79 mmol) in N,N-dimethylformamide (1.5 ml) in air at 15° C. The reaction mixture was stirred at 15° C. overnight. Water (30 ml) was added and the reaction mixture extracted with ethyl acetate (30 ml×3). The organic phases were dried with Na2SO4 and concentrated. The residue was purified by pre-HPLC (instrument: Gilson-281, Column: WATERS XBRIDGE 30-100 MM 5 UM, Mobile Phase: A: 0.04% NH3H2O B: CH3CN, Flow rate: 30.0 ml/L, Gradient: 0-10 min, B=30-38% RT=P1: 7.0 min; P2: 9.5 min) to yield the title compound as a white solid. 20 mg.

Workup

  1. extractionthe reaction mixture extracted with ethyl acetate (30 ml×3)
  2. dry with materialThe organic phases were dried with Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified by pre-HPLC (instrument
  5. custom0-10 min, B=30-38% RT=P1
  6. custom7.0 min

Sources & evidence

ORD record
ord-0f4a96eedfd74d53a4bb52cb9aafd73f
Source dataset
uspto-grants-2014_07
Patent number
US08778939B2

Reaction notes

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