Citric Acid → HCID 131727651, compound

HRID 1817714Notes

Reaction equation

HRID 1817714 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[CH2:20][NH:19][CH2:18][CH2:17][C:10]=3[N:11]=[C:12]([CH:14]([CH3:16])[CH3:15])[N:13]=2)=[CH:4][CH:3]=1.[C:21]([OH:33])(=[O:32])[CH2:22][C:23]([CH2:28][C:29]([OH:31])=[O:30])([C:25]([OH:27])=[O:26])[OH:24]>CCO.CCOCC>[C:21]([OH:33])(=[O:32])[CH2:22][C:23]([CH2:28][C:29]([OH:31])=[O:30])([C:25]([OH:27])=[O:26])[OH:24].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[CH2:20][NH:19][CH2:18][CH2:17][C:10]=3[N:11]=[C:12]([CH:14]([CH3:16])[CH3:15])[N:13]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 311Citric AcidHCID 16062389HCID 16062389, compound

Product 1

HCID 131727651HCID 131727651, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
50 °C

Procedure

A solution of crude 4-(4-fluoro-phenyl)-2-isopropyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (Example 164) in EtOH (1 L) was treated with citric acid (71 g, 0.37 mol). The solution was warmed to 50° C. to form a homogeneous solution, then was cooled to rt and stirred for 16 h. The mixture was diluted with Et2O (750 mL) and was stirred for 1 h. The precipitated white solid was collected by filtration and washed with cold EtOH (ca. 100 mL). The white solid was dried in a vacuum oven at 55° C. to give an off-white solid (157.3 g, 50% overall yield). HPLC: RT=6.86 min. MS (ESI): exact mass calcd. for C16H18FN3, 271.15; m/z found, 271.9 [M+H]+. 1H NMR (D2O): 7.49-7.43 (m, 2H), 7.27-7.19 (m, 2H), 4.28 (s, 2H), 3.60 (t, J=6.5, 2H), 3.20 (t, J=6.5, 2H), 3.11 (sept, J=6.9, 1H), 2.77 (d, J=15.4, 2H), 2.65 (d, J=15.4, 2H), 1.23 (d, J=6.9, 6H). 13C NMR (D2O): 176.59, 172.69, 171.99, 162.59 (d, JC-F=11.6), 160.67, 159.41, 129.42, 128.53 (d, JC-F=8.8), 115.91, 113.89 (d, JC-F=22.4), 71.78, 41,61, 40.10, 38.77, 34.78, 25.33, 18.64. The compounds in Examples 166-167 were prepared using methods analogous to those described in the preceding examples.

Workup

  1. customto form a homogeneous solution
  2. temperaturewas cooled to rt
  3. stirringwas stirred for 1 h
  4. filtrationThe precipitated white solid was collected by filtration
  5. washwashed with cold EtOH (ca. 100 mL)
  6. customThe white solid was dried in a vacuum oven at 55° C.
  7. customto give
  8. customan off-white solid (157.3 g, 50% overall yield)
  9. customThe compounds in Examples 166-167 were prepared

Sources & evidence

ORD record
ord-53c2326c550e4d13978a0469ef1b6c97
Source dataset
uspto-grants-2009_10
Patent number
US07598255B2

Reaction notes

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