Trifluoroacetic acid → HCID 178476876, compound

HRID 511466Notes

Reaction equation

HRID 511466 reaction equation
C([O:5][P:6]([O:13][C@H:14]1[CH2:19][CH2:18][C@H:17]([C:20]2[CH:21]=[CH:22][C:23]([NH:31][C:32]3[C:37]([C:38]([F:41])([F:40])[F:39])=[CH:36][N:35]=[C:34]([NH:42][C:43]4[CH:57]=[CH:56][C:46]([CH2:47][P:48](=[O:55])([O:52][CH2:53][CH3:54])[O:49][CH2:50][CH3:51])=[CH:45][C:44]=4[O:58][CH3:59])[N:33]=3)=[C:24]3[C:28]=2[CH2:27][N:26]([CH3:29])[C:25]3=[O:30])[CH2:16][CH2:15]1)([O:8]C(C)(C)C)=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O>C1COCC1>[CH3:59][O:58][C:44]1[CH:45]=[C:46]([CH:56]=[CH:57][C:43]=1[NH:42][C:34]1[N:33]=[C:32]([NH:31][C:23]2[CH:22]=[CH:21][C:20]([C@H:17]3[CH2:16][CH2:15][C@H:14]([O:13][P:6]([OH:7])([OH:8])=[O:5])[CH2:19][CH2:18]3)=[C:28]3[C:24]=2[C:25](=[O:30])[N:26]([CH3:29])[CH2:27]3)[C:37]([C:38]([F:40])([F:41])[F:39])=[CH:36][N:35]=1)[CH2:47][P:48](=[O:55])([O:52][CH2:53][CH3:54])[O:49][CH2:50][CH3:51]

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, 6 H), 1.41-1.46 (m, 2 H), 1.66-1.76 (m, 4 H), 2.12-2.15 (m, 2 H), 2.49 (m, 1 H), 3.04 (s, 3 H), 3.29 (d, J=21.20 Hz, 2 H), 3.73 (s, 3 H), 3.96-4.03 (m, 4 H), 4.12 (m, 1 H), 4.47 (s, 2 H), 6.89 (d, J=7.6 Hz, 1 H), 7.05 (s, 1 H), 7.36 (d, J=8.8 Hz, 1 H), 7.43 (s, br, 1 H), 8.36 (d, J=0.8 Hz, 1 H), 8.98 (s, 1 H), 10.54 (s, 1 H). 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-a8ddd765ab0c4be6998d46f8034dfe87
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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