p-Toluenesulfonic acid monohydrate → HCID 78324585, compound

HRID 2170168Notes

Reaction equation

HRID 2170168 reaction equation
[CH2:1]([NH:8][C:9]1[C:14]2=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:16]=[CH:17][N:13]2[N:12]=[C:11]([C:24]2[CH:25]=[N:26][CH:27]=[C:28]([CH:30]3[CH2:35][O:34]C(C)(C)[O:32][CH2:31]3)[CH:29]=2)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO.C(=O)(O)[O-].[Na+]>[CH2:1]([NH:8][C:9]1[C:14]2=[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:16]=[CH:17][N:13]2[N:12]=[C:11]([C:24]2[CH:29]=[C:28]([CH:30]([CH2:35][OH:34])[CH2:31][OH:32])[CH:27]=[N:26][CH:25]=2)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 90386092HCID 90386092, compound

Product 1

HCID 78324585HCID 78324585, compoundYield 63.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of N-benzyl-2-(5-(2,2-dimethyl-1,3-dioxan-5-yl)pyridin-3-yl)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-4-amine (60.0 mg, 0.122 mmol) in methanol (15 mL) was added p-toluenesulfonic acid monohydrate (12.0 mg, 0.0610 mmol) and stirred at ambient temperature for 2 h. Reaction mixture was diluted with saturated sodium bicarbonate solution (50 mL) and extracted into DCM (2×50 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The resulting residue was purified by preparative HPLC (Condition B-73 as described in general methods) to get 2-(5-(4-(benzylamino)-5-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridin-3-yl)propane-1,3-diol (35.0 mg, 63.5%). LCMS Condition B-12: retention time 2.00, [M+1]=452.2. HPLC Condition B-4: retention time 7.22, purity 97.89%. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.93-2.96 (m, 1H), 3.68-3.77 (m, 4H), 4.69 (br s, 2H), 4.80 (d, J=5.6 Hz, 2H), 6.69 (t, J=5.6 Hz, 1H), 6.79 (d, J=2.8 Hz, 1H), 7.23-7.27 (m, 1H), 7.32-7.41 (m, 5H), 7.46-7.55 (m, 4H), 7.90 (d, J=2.8 Hz, 1H), 8.36 (t, J=2.4 Hz, 1H), 8.51 (d, J=2.0 Hz, 1H), 9.19 (d, J=2.0 Hz, 1H).

Workup

  1. customReaction mixture
  2. extractionextracted into DCM (2×50 mL)
  3. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe resulting residue was purified by preparative HPLC (Condition B-73 as described in general methods)

Sources & evidence

ORD record
ord-cd6504916dd340f8b5269d896122c696
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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