Trifluoroacetic acid → HCID 58577824, compound

HRID 473962Notes

Reaction equation

HRID 473962 reaction equation
FC(F)(F)C(O)=O.C([SiH](CC)CC)C.[CH2:15]([CH:17]1[O:22][C:21]2[CH:23]=[C:24]([C:27]3[CH:28]=[N:29][C:30]([N:33]4[CH2:37][CH2:36][CH:35]([CH2:38][C:39]([O:41]CCCC)=[O:40])[CH2:34]4)=[N:31][CH:32]=3)[CH:25]=[CH:26][C:20]=2[N:19]([C:46](=[O:54])[NH:47][C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH2:18]1)[CH3:16]>C(Cl)Cl>[CH2:15]([CH:17]1[O:22][C:21]2[CH:23]=[C:24]([C:27]3[CH:28]=[N:29][C:30]([N:33]4[CH2:37][CH2:36][CH:35]([CH2:38][C:39]([OH:41])=[O:40])[CH2:34]4)=[N:31][CH:32]=3)[CH:25]=[CH:26][C:20]=2[N:19]([C:46](=[O:54])[NH:47][C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH2:18]1)[CH3:16]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 131731161HCID 131731161, compound

Product 1

HCID 58577824HCID 58577824, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.109 mL, 1.43 mmol) and triethylsilane (44 μL, 0.28 mmol) were successively added at room temperature to a solution of crude ted-butyl 2-(1-(5-(2-ethyl-4-(phenylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyrimidin-2-yl)pyrrolidin-3-yl)acetate B-8 (59.0 mg, 0.11 mmol) in anhydrous methylene chloride (0.25 mL) under an atmosphere of argon. The reaction mixture was stirred at room temperature for 12 h, then concentrated to dryness under reduced pressure. The crude residue was purified by flash column chromatography on C18 reverse phase (water:acetonitrile gradient with 0.05% formic acid) to give 2-(1-(5-(2-ethyl-4-(phenylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyrimidin-2-yl)pyrrolidin-3-yl)acetic acid B-9 (22.3 mg, Yield=42% over 2 steps). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.01 (t, J=Hz, 3H), 1.63-1.74 (m, 3H), 2.12-2.18 (m, 1H), 2.42 (d, J=7.25 Hz, 2H), 2.52-2.64 (m, 1H), 3.15 (dd, J=7.88, 10.88 Hz, 1H), 3.46 (dd, J=7.88, 12.60 Hz, 1H), 3.48 (t, J=7.56 Hz, 1H), 3.63-3.69 (m, 1H), 3.80 (dd, J=7.41, 11.35 Hz, 1H), 4.03 (br d, J=13.08 Hz, 1H), 4.16 (q, J=6.69 Hz, 1H), 7.00 (t, J=7.41 Hz, 1H), 7.15 (br d, J=8.67 Hz, 1H), 7.18 (s, 1H), 7.29 (t, J=7.41 Hz, 2H), 7.50 (d, J=8.36 Hz, 2H), 7.51 (d, J=8.83 Hz, 1H), 8.66 (s, 2H), 9.14 (s, 1H), 12.22 (br s, 1H); MS (ESI) [M+1]+ 488.

Workup

  1. concentrationconcentrated to dryness under reduced pressure
  2. customThe crude residue was purified by flash column chromatography on C18 reverse phase (water:acetonitrile gradient with 0.05% formic acid)

Sources & evidence

ORD record
ord-4d6d323dbdac43848f1ec14e7f172b4e
Source dataset
uspto-grants-2014_01
Patent number
US08637507B2

Reaction notes

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