Hydrochloric Acid → 4-(Benzyloxy)-1-(5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one hydrochloride

HRID 930610Notes

Reaction equation

HRID 930610 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:16]=[CH:17][C:18]3[C:19]4[CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25][C:20]=4[N:21]([CH3:24])[C:22]=3[CH:23]=2)[C:11](=[O:36])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:37]>CO.CCOCC>[ClH:37].[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:16]=[CH:17][C:18]3[C:19]4[CH2:28][NH:27][CH2:26][CH2:25][C:20]=4[N:21]([CH3:24])[C:22]=3[CH:23]=2)[C:11](=[O:36])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 57950332tert-Butyl 7-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate

Product 1

HCID 441947474-(Benzyloxy)-1-(5-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-7-yl)pyridin-2(1H)-one hydrochlorideYield 85%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Procedure

tert-Butyl 7-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (12.0 g, 24.7 mmol) was dissolved in MeOH (100 mL), and 2 N HCl in Et2O (300 mL) was added. The reaction was allowed to proceed for 18 h. The mixture was concentrated, and the residue was partitioned between CH2Cl2 and sat. Na2CO3 solution. The organic phase was removed, and the aqueous phase was back extracted with CH2Cl2. The combined organic extracts were dried over Na2SO4, filtered and concentrated to dryness providing the free base of the title compound (8.1 g, 85%) as a yellow solid. A portion of the free base was converted to the HCl salt for biological testing. Free base: 1H NMR (500 MHz, CDCl3) δ 7.47-7.34 (m, 6H), 7.32-7.28 (m, 2H), 6.98 (d, J=7.1 Hz, 1H), 6.07 (d, J=2.6 Hz, 1H), 6.04 (dd, J=7.5, 2.6 Hz, 1H), 5.05 (s, 2H), 4.15 (s, 2H), 3.61 (s, 3H), 3.34 (br s, 2H), 2.78 (br s, 2H). HCl salt: melting point (mp) 296-302° C.; 1H NMR (500 MHz, CD3OD) δ 7.61-7.57 (2×d, 2H), 7.47-7.46 (m, 3H), 7.43-7.40 (m, 2H), 7.37-7.34 (m, 1H), 7.05 (dd, J=8.3, 1.7 Hz, 1H), 6.33 (dd, J=7.5, 2.7 Hz, 1H), 6.16 (d, J=2.6 Hz, 1H), 5.19 (s, 2H), 4.57 (s, 2H), 3.73 (s, 3H), 3.67 (t, J=6.2 Hz, 2H), 3.20 (t, J=6.1 Hz, 2H); ESI MS m/z 386 [M+H]+; HPLC (Method A) 95.7% (AUC), tR=13.6 min.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between CH2Cl2 and sat. Na2CO3 solution
  3. customThe organic phase was removed
  4. extractionthe aqueous phase was back extracted with CH2Cl2
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-d4f15710d245455a953dfa4461b49700
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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