Trifluoroacetic acid → (R)-1-(4-(6-(5-isopropyl-2-methylphenyl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-yl)ethanone

HRID 80778Notes

Reaction equation

HRID 80778 reaction equation
[C:1](O)([C:3](F)(F)F)=[O:2].[CH:8]([C:11]1[CH:12]=[CH:13][C:14]([CH3:54])=[C:15]([N:17]2[CH2:53][CH2:52][C:20]3[N:21]=[C:22]([C:32]4[CH:40]=[CH:39][CH:38]=[C:37]5[C:33]=4[C:34]([CH3:51])=[CH:35][N:36]5[S:41]([C:44]4[CH:50]=[CH:49][C:47]([CH3:48])=[CH:46][CH:45]=4)(=[O:43])=[O:42])[N:23]=[C:24]([N:25]4[CH2:30][CH2:29][NH:28][CH2:27][C@H:26]4[CH3:31])[C:19]=3[CH2:18]2)[CH:16]=1)([CH3:10])[CH3:9].C(OC(=O)C)(=O)C.CCN(C(C)C)C(C)C>C(Cl)Cl.CCOC(C)=O>[CH:8]([C:11]1[CH:12]=[CH:13][C:14]([CH3:54])=[C:15]([N:17]2[CH2:53][CH2:52][C:20]3[N:21]=[C:22]([C:32]4[CH:40]=[CH:39][CH:38]=[C:37]5[C:33]=4[C:34]([CH3:51])=[CH:35][N:36]5[S:41]([C:44]4[CH:45]=[CH:46][C:47]([CH3:48])=[CH:49][CH:50]=4)(=[O:42])=[O:43])[N:23]=[C:24]([N:25]4[CH2:30][CH2:29][N:28]([C:1](=[O:2])[CH3:3])[CH2:27][C@H:26]4[CH3:31])[C:19]=3[CH2:18]2)[CH:16]=1)([CH3:10])[CH3:9]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 71240674(R)-6-(5-isopropyl-2-methylphenyl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-4-(2-methylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Product 1

HCID 71240550(R)-1-(4-(6-(5-isopropyl-2-methylphenyl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-yl)ethanone

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The TFA salt of (R)-6-(5-isopropyl-2-methylphenyl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-4-(2-methylpiperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (62 mg, 0.095 mmol) was dissolved in DCM (5 mL) and acetic anhydride (0.014 mL, 0.143 mmol) and DIEA (0.133 mL, 0.764 mmol) were added. The reaction was stirred at rt for 45 min and diluted with EtOAc, and washed successively with sat NaHCO3 and brine. The organic layer was then dried over Na2SO4 and filtered. After concentration, the resulting residue was purified by FCC (60-90% EtOAc/heptane) to provide (R)-1-(4-(6-(5-isopropyl-2-methylphenyl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-yl)ethanone. MS (ESI+) m/z 691.4 (M+H)+.

Workup

  1. washwashed successively with sat NaHCO3 and brine
  2. dry with materialThe organic layer was then dried over Na2SO4
  3. filtrationfiltered
  4. concentrationAfter concentration
  5. customthe resulting residue was purified by FCC (60-90% EtOAc/heptane)

Sources & evidence

ORD record
ord-d97f38b079554c3c89b7e13ce170f177
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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