Formaldehyde → Pentafluorophenyl o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzoate

HRID 1289224Notes

Reaction equation

HRID 1289224 reaction equation
C=O.[F:3][C:4]1[CH:23]=[C:22]([NH:24][CH:25]2[C:29]3[CH:30]=[C:31]4[C:36](=[CH:37][C:28]=3[CH2:27][CH2:26]2)[N:35]=[C:34]([CH3:38])[N:33]([CH2:39][O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43])[C:32]4=[O:47])[CH:21]=[CH:20][C:5]=1[C:6]([O:8][C:9]1[C:14]([F:15])=[C:13]([F:16])[C:12]([F:17])=[C:11]([F:18])[C:10]=1[F:19])=[O:7].[C:48]([BH3-])#N.[Na+].O>C(O)(=O)C>[F:3][C:4]1[CH:23]=[C:22]([N:24]([CH3:48])[CH:25]2[C:29]3[CH:30]=[C:31]4[C:36](=[CH:37][C:28]=3[CH2:27][CH2:26]2)[N:35]=[C:34]([CH3:38])[N:33]([CH2:39][O:40][C:41](=[O:46])[C:42]([CH3:43])([CH3:45])[CH3:44])[C:32]4=[O:47])[CH:21]=[CH:20][C:5]=1[C:6]([O:8][C:9]1[C:10]([F:19])=[C:11]([F:18])[C:12]([F:17])=[C:13]([F:16])[C:14]=1[F:15])=[O:7]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 19066345Pentafluorophenyl o-fluoro-p-[N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzoate

Product 1

HCID 19066320Pentafluorophenyl o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzoate

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

An aqueous solution of formaldehyde (37% weight/volume, 17.55 ml) was added dropwise during 15 minutes to a stirred solution of pentafluorophenyl o-fluoro-p-[N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzoate (13 g), prepared as described in Example 1, in glacial acetic acid (100 ml). The mixture was stirred at ambient temperature for 1 hour. Sodium cyanoborohydride (1.36 g) was added portionwise during 30 minutes and the resultant mixture was stirred at ambient temperature for 2 hours. The mixture was poured onto a mixture of ice and water (500 ml) and extracted with ethyl acetate. The organic phase was dried (MgSO4) and evaporated. The product was purified by column chromatography using increasingly polar mixtures of hexane and ethyl acetate as eluant. There was thus obtained pentafluorophenyl o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzoate (11 g);

Workup

  1. customprepared
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic phase was dried (MgSO4)
  4. customevaporated
  5. customThe product was purified by column chromatography
  6. temperatureusing increasingly polar mixtures of hexane and ethyl acetate as eluant

Sources & evidence

ORD record
ord-437402b1b15541b4b1c2f3756e2da3c2
Source dataset
uspto-grants-1998_05
Patent number
US05747499

Reaction notes

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