Trimethylsilyl iodide → HCID 59459405, compound

HRID 1874260Notes

Reaction equation

HRID 1874260 reaction equation
[F:1][C:2]([F:48])([F:47])[CH:3]([NH:36]C(=O)OCC1C=CC=CC=1)[C:4]([NH:6][C@@:7]([C:22]1[CH:27]=[C:26]([O:28][C:29]([F:34])([F:33])[CH:30]([F:32])[F:31])[CH:25]=[C:24]([F:35])[CH:23]=1)([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5].[Si](I)(C)(C)C>C(Cl)Cl>[NH2:36][CH:3]([C:2]([F:47])([F:48])[F:1])[C:4]([NH:6][C@@:7]([C:22]1[CH:27]=[C:26]([O:28][C:29]([F:34])([F:33])[CH:30]([F:32])[F:31])[CH:25]=[C:24]([F:35])[CH:23]=1)([C:15]1[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=1)[CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)=[O:5]

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 58898096HCID 58898096, compound

Product 1

HCID 59459405HCID 59459405, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of benzyl 1,1,1-trifluoro-3-((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethylamino)-3-oxopropan-2-ylcarbamate (10 mg, 0.014 mmol) in CH2Cl2 (0.5 mL) was added TMSI (18 mg, 0.094 mmol). The reaction mixture was sealed and stirred at rt for 20 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by prep HPLC (Phenomenex Luna AXIA 5μ 21.2×100 mm, 10%-90% ACN/H2O containing 0.1% TFA, flow rate 20 mL/min, gradient time 10 min) to yield 2-amino-3,3,3-trifluoro-N—((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)propanamide (Example 324) as a white solid (5 mg, 65% yield). HPLC: RT=1.90 min [M+H] 551.5 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); 1H NMR (400 MHz, CDCl3) δ ppm 7.82-7.85, m, 1H, 7.19-7.23, m, 1H, 7.11-7.17, m, 2H, 7.07-7.11, m, 1H, 6.98-7.03, m, 3 H, 6.89-6.93, m, 2H, 6.80-6.86, m, 1H, 6.61-6.64, m, 2H, 5.73-5.99, t, J=52, 1H, 4.00-4.03, J=12, d, 1H, 3.98, m, 1H, 3.63-3.67, d, J=12, 1H;

Workup

  1. customThe reaction mixture was sealed
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customthe residue was purified by prep HPLC (Phenomenex Luna AXIA 5μ 21.2×100 mm, 10%-90% ACN/H2O containing 0.1% TFA, flow rate 20 mL/min, gradient time 10 min)

Sources & evidence

ORD record
ord-33d64092a4354a40b34cbb5524d88459
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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