Formic Acid → HCID 68283489, compound

HRID 1469563Notes

Reaction equation

HRID 1469563 reaction equation
[CH3:1][N:2]1[CH2:24][CH2:23][C:5]2[N:6]([CH2:14][CH:15]([C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[OH:16])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.C=O.[CH:27](O)=[O:28]>>[OH:28][CH2:27][C:11]1[C:12]2[C:4]3[CH2:3][N:2]([CH3:1])[CH2:24][CH2:23][C:5]=3[N:6]([CH2:14][CH:15]([C:17]3[CH:18]=[CH:19][N:20]=[CH:21][CH:22]=3)[OH:16])[C:7]=2[CH:8]=[CH:9][C:10]=1[CH3:13]

Participants

4

Reactant 3

HCID 284Formic AcidHCID 712FormaldehydeHCID 49779650HCID 49779650, compound

Product 1

HCID 68283489HCID 68283489, compoundYield 7.1%

Procedure

2-(2,8-Dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-(pyridin-4-yl)ethanol (350 mg, 1 mmol), formaldehyde (37%, 0.89 g, 10 mmol) and formic acid (922 mg, 20 mmol) was stirred at 100° C. for 12 h. The progress of the reaction was monitored by TLC and LCMS. The reaction mixture was washed with saturated sodium bicarbonate and extracted with DCM (2×25 mL). The combined organic layer was washed with water (5×25 mL) dried over anhydrous sodium sulfate and concentrated under vacuum to obtain the crude product, which was subjected to preparative HPLC to obtain 25 mg of 2-(9-(hydroxymethyl)-2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-(pyridin-4-yl)ethanol. 1H NMR (CDCl3, freebase) δ (ppm): 8.56 (d, 2H), 7.29 (d, 2H), 7.12 (d, 1H), 6.98 (d, 1H), 4.9 (dd, 1H), 4.79 (q, 2H), 4.13 (m, 2H), 3.78 (d, 1H), 3.72 (d, 1H), 3.0 (m, 1H), 2.8 (m, 1H), 2.67 (m, 2H), 2.49 (s, 3H), 2.32 (s, 3H). Separation by chiral HPLC provided diastereomers II-150a-d.

Workup

  1. washThe reaction mixture was washed with saturated sodium bicarbonate
  2. extractionextracted with DCM (2×25 mL)
  3. washThe combined organic layer was washed with water (5×25 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customto obtain the crude product, which

Sources & evidence

ORD record
ord-66d370507e804c2289bf194e685897dd
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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