Trifluoroacetic acid → HCID 178476876, compound

HRID 1948033Notes

Reaction equation

HRID 1948033 reaction equation
[CH2:1]([O:3][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3[CH:32]=[CH:31][C:30]([C@H:33]4[CH2:38][CH2:37][C@H:36]([O:39][P:40]([O:47]C(C)(C)C)([O:42]C(C)(C)C)=[O:41])[CH2:35][CH2:34]4)=[C:29]4[C:25]=3[C:26](=[O:53])[N:27]([CH3:52])[CH2:28]4)[C:20]([C:54]([F:57])([F:56])[F:55])=[CH:19][N:18]=2)=[C:12]([O:58][CH3:59])[CH:11]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].C(O)(C(F)(F)F)=O>C1COCC1>[CH2:6]([O:5][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3[CH:32]=[CH:31][C:30]([C@H:33]4[CH2:34][CH2:35][C@H:36]([O:39][P:40]([OH:42])([OH:47])=[O:41])[CH2:37][CH2:38]4)=[C:29]4[C:25]=3[C:26](=[O:53])[N:27]([CH3:52])[CH2:28]4)[C:20]([C:54]([F:57])([F:55])[F:56])=[CH:19][N:18]=2)=[C:12]([O:58][CH3:59])[CH:11]=1)(=[O:8])[O:3][CH2:1][CH3:2])[CH3:7]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178476875HCID 178476875, compound2×

Product 1

HCID 178476876HCID 178476876, compoundYield 95.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of diethyl[4-({4-[(7-{trans-4-[(di-tert-butoxyphosphoryl)oxy]cyclohexyl}-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)-3-methoxybenzyl]phosphonate (Compound 228A, 38.5 mg, 0.044 mmol) in THF (2 mL) was added TFA (1 mL). The reaction mixture was stirred at rt for 1 h. Solvents were then removed in vacuo and the residue was purified by MDP (formic acid conditions) to obtain 31.9 mg of the desired product (yield: 95%). 1H NMR (DMSO-d6, 400 MHz): δ=1.19 (t, J=7.6 Hz, 6H), 1.41-1.46 (m, 2H), 1.66-1.76 (m, 4H), 2.12-2.15 (m, 2H), 2.49 (m, 1H), 3.04 (s, 3H), 3.29 (d, J=21.20 Hz, 2H), 3.73 (s, 3H), 3.96-4.03 (m, 4H), 4.12 (m, 1H), 4.47 (s, 2H), 6.89 (d, J=7.6 Hz, 1H), 7.05 (s, 1H), 7.36 (d, J=8.8 Hz, 1H), 7.43 (s, br, 1H), 8.36 (d, J=0.8 Hz, 1H), 8.98 (s, 1H), 10.54 (s, 1H). MS (ES+): m/z 758.21 [MH+]. HPLC: tR=1.27 min (UPLC TOF, polar—3 min).

Workup

  1. customSolvents were then removed in vacuo
  2. customthe residue was purified by MDP (formic acid conditions)

Sources & evidence

ORD record
ord-b3a75b26ab654e25a95cf04c9474060c
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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