Triethylamine → HCID 69054647, compound

HRID 731914Notes

Reaction equation

HRID 731914 reaction equation
[F:1][C:2]1[N:12]=[CH:11][C:5]2[N:6]=[CH:7][NH:8][C:9](=O)[C:4]=2[CH:3]=1.O=S(Cl)Cl.CCN(CC)CC.[C:24]([O:28][C:29](=[O:45])[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([O:36][C:37]2[CH:42]=[CH:41][C:40]([NH2:43])=[CH:39][C:38]=2[CH3:44])[CH:31]=1)([CH3:27])([CH3:26])[CH3:25]>ClCCCl.CN(C=O)C>[C:24]([O:28][C:29](=[O:45])[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([O:36][C:37]2[CH:42]=[CH:41][C:40]([NH:43][C:9]3[C:4]4[CH:3]=[C:2]([F:1])[N:12]=[CH:11][C:5]=4[N:6]=[CH:7][N:8]=3)=[CH:39][C:38]=2[CH3:44])[CH:31]=1)([CH3:27])([CH3:26])[CH3:25]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 53439210tert-Butyl 3-(4-amino-2-methylphenoxy)benzoateHCID 1354173706-fluoropyrido[3,4-d]pyrimidin-4-ol

Product 1

HCID 69054647HCID 69054647, compoundYield 80.8%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 6-Fluoro-3H-pyrido[3,4-d]pyrimidin-4-one (0.5 g, 3.05 mmol), SOCl2 (3.63 g, 30.5 mmol), and DMF (0.2 mL) in DCE (20 mL) was heated to reflux for 12 h. The reaction was then concentrated and the resulting dark residue was dissolved in t-BuOH/DCE 1:1 (20 mL), NEt3 (0.34 g, 3.36 mmol) and 3-(4-Amino-2-methyl-phenoxy)-benzoic acid tert-butyl ester (0.91 g, 3.05 mmol) were added, the resulting solution was heated to reflux for 5 h. The reaction was concentrated, the residue was dissolved in EtOAc and washed 2× water then the organic layer was dried over Na2SO4. Purification by flash column chromatography (Hexane/Ethyl Acetate 4:6) gave the title compound as a yellow solid (1.1 g, 80%). LRMS: 447.3/391.2 (MH+). 1H NMR (DMSO-d6, 400 MHz): δ 10.03 (s, 1H), δ 8.90 (s, 1H), δ 8.65 (s, 1H), δ 8.23 (s, 1H), δ 7.803 (d, 1H), δ 7.73 (dd, J=6.23, 2.49, 1H), δ 7.58 (d, 1H) δ 7.45 (t, J=7.89, 1H), δ 7.31-7.32 (m, 1H), δ 7.14-7.16 (m, 1H), δ 7.027 (d, J=8.72, 1H), δ 2.16 (s, 3H), δ 1.48 (s, 9H).

Workup

  1. temperatureto reflux for 12 h
  2. concentrationThe reaction was then concentrated
  3. dissolutionthe resulting dark residue was dissolved in t-BuOH/DCE 1:1 (20 mL)
  4. temperaturethe resulting solution was heated
  5. temperatureto reflux for 5 h
  6. concentrationThe reaction was concentrated
  7. dissolutionthe residue was dissolved in EtOAc
  8. washwashed 2× water
  9. dry with materialthe organic layer was dried over Na2SO4
  10. customPurification by flash column chromatography (Hexane/Ethyl Acetate 4:6)

Sources & evidence

ORD record
ord-e099b3918245463d9336b4719e7a2c7e
Source dataset
uspto-grants-2009_09
Patent number
US07585869B2

Reaction notes

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