Toluene → HCID 58213531, compound

HRID 1479576Notes

Reaction equation

HRID 1479576 reaction equation
[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:24]=[CH:23][C:17]([C:18](OCC)=[O:19])=[CH:16][C:15]=3[CH3:25])=[CH:7][C:6]=2[C:5]2[CH:26]=[CH:27][C:28]([CH3:30])=[CH:29][C:4]=2[N:3]=1.CC(C[AlH]CC(C)C)C.C1(C)C=CC=CC=1.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1COCC1>[NH2:1][C:2]1[C:11]2[N:10]=[CH:9][C:8]([CH2:12][CH2:13][C:14]3[CH:24]=[CH:23][C:17]([CH2:18][OH:19])=[CH:16][C:15]=3[CH3:25])=[CH:7][C:6]=2[C:5]2[CH:26]=[CH:27][C:28]([CH3:30])=[CH:29][C:4]=2[N:3]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 9357Potassium Sodium TartrateHCID 14487Diisobutylaluminum hydrideHCID 53339050HCID 53339050, compound

Product 1

HCID 58213531HCID 58213531, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)-3-methylbenzoate (from Example 74) (1.0 eq.) in THF (0.1M) at −78° C. was added 1.0 M DIBAL-H in toluene (10 eq.) and warmed to room temperature over 2 hours. 1.5 M Rochelle salt aqueous solution was added slowly to quench the reaction followed by addition of EA, and the mixture was stirred for 45 minutes. The two phases were separated, and the aqueous layer was extracted twice with EA. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude material was purified by RP-HPLC using a 10-50% MeCN in water gradient followed by extraction in DCM to give (4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)-3-methylphenyl)methanol. 1H NMR (Acetone-d6): δ 8.77 (s, 1H), 8.71 (s, 1H), 8.25 (d, 1H), 7.41 (s, 1H), 7.10-7.15 (m, 4H), 6.5 (br, 2H), 4.54 (s, 2H), 4.05 (br, 1H), 3.08-3.18 (m, 4H), 2.44 (s, 3H), 2.31 (s, 3H). LRMS [M+H]=358.2

Workup

  1. customto quench the reaction
  2. additionfollowed by addition of EA
  3. customThe two phases were separated
  4. extractionthe aqueous layer was extracted twice with EA
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationconcentrated en vaccuo
  8. customThe crude material was purified by RP-HPLC
  9. extractionfollowed by extraction in DCM

Sources & evidence

ORD record
ord-574da6d48dca42aa9bf161fea3740478
Source dataset
uspto-grants-2016_08
Patent number
US09408907B2

Reaction notes

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