Hydrochloric Acid → HCID 68460474, compound

HRID 2387486Notes

Reaction equation

HRID 2387486 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[N:20]([CH2:24][C:25](OC)=O)[N:19]=[CH:18]3)[C:11](=[O:29])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:30]([NH2:33])[CH2:31][NH2:32].[Al](C)(C)C.[ClH:38]>C1(C)C=CC=CC=1.O.C(OCC)(=O)C.CCOCC>[ClH:38].[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[N:20]([CH2:24][C:25]2[NH:32][CH2:31][CH2:30][N:33]=2)[N:19]=[CH:18]3)[C:11](=[O:29])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 3301EthylenediamineHCID 16682925TrimethylaluminumHCID 59293408HCID 59293408, compound

Product 1

HCID 68460474HCID 68460474, compoundYield 14%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl 2-(5-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-1H-indazol-1-yl)acetate (100 mg, 0.217 mmol) in toluene (0.5 mL) was treated with ethane-1,2-diamine (24 mg, 0.40 mmol) and Al(CH3)3 (0.2 mL, 2 M in toluene, 0.4 mmol) at 0° C. under nitrogen. Then, the reaction mixture was heated to reflux. After stirring at reflux for 16 h, the reaction mixture was diluted with H2O (20 mL) and extracted with CH2Cl2 (2×25 mL). The organics were dried (Na2SO4), filtered and concentrated. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH/NH4OH, 40:1:0.05 to 20:1:0.15) provided the free base. This was dissolved in ethyl acetate (0.3 mL) and treated with 1 equivalent of 1 M HCl in Et2O. The resulting mixture was filtered to provide the title compound (13.5 mg, 14%) as a yellow solid melting point (mp) 164-166° C.; 1H NMR (500 MHz, DMSO-d6) δ 10.22 (s, 1H), 8.31 (d, J=0.7 Hz, 1H), 7.84 (d, J=8.9 Hz, 1H), 7.82 (d, J=16 Hz, 1H), 7.59 (d, J=7.6 Hz, 1H), 7.49-7.36 (m, 6H), 6.12 (dd, J=7.6, 2.7 Hz, 1H), 5.99 (d, J=2.7 Hz, 1H), 5.70 (s, 2H), 5.16 (s, 2H), 3.87 (s, 4H); ESI MS m/z 400 [M+H]+.

Workup

  1. temperatureThen, the reaction mixture was heated to reflux
  2. temperatureat reflux for 16 h
  3. extractionextracted with CH2Cl2 (2×25 mL)
  4. dry with materialThe organics were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH/NH4OH, 40:1:0.05 to 20:1:0.15)
  8. customprovided the free base
  9. filtrationThe resulting mixture was filtered

Sources & evidence

ORD record
ord-4329c30cf1ed49a3abd9a4c8af50c880
Source dataset
uspto-grants-2012_09
Patent number
US08268868B2

Reaction notes

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