Isopropyl iodide → HCID 16743761, compound

HRID 1993627Notes

Reaction equation

HRID 1993627 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]([C:27]2[CH:32]=[C:31]([O:33][C:34]([F:39])([F:38])[CH:35]([F:37])[F:36])[CH:30]=[C:29]([F:40])[CH:28]=2)([NH:16][C:17]2[S:18][C:19]([CH3:26])=[C:20]([C:22]([F:25])([F:24])[F:23])[N:21]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][C:3]=1[OH:41].C([O-])([O-])=O.[K+].[K+].I[CH:49]([CH3:51])[CH3:50]>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]([NH:16][C:17]2[S:18][C:19]([CH3:26])=[C:20]([C:22]([F:23])([F:25])[F:24])[N:21]=2)([C:27]2[CH:32]=[C:31]([O:33][C:34]([F:38])([F:39])[CH:35]([F:37])[F:36])[CH:30]=[C:29]([F:40])[CH:28]=2)[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:4][C:3]=1[O:41][CH:49]([CH3:51])[CH3:50]

Participants

5

Reactant 3

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 16743585HCID 16743585, compound

Product 1

HCID 16743761HCID 16743761, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-2-fluoro-5-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(5-methyl-4-(trifluoromethyl)thiazol-2-ylamino)-2-phenylethyl)phenol (16 mg, 0.026 mmol) in DMF (0.5 mL) was added K2CO3 (8 mg, 0.058 mmol), followed by the addition of 2-iodopropane (5 mg, 0.03 mmol). The reaction vessel was sealed and stirred at room temperature for 18 h. The solid was removed by filtration and the filtrate was purified by preparative HPLC Phenomenex AXIA Luna S5 30×75 mm Ballistic column 50-100% ACN (90% in water, 0.1% TFA) gradient over 10 min with flow rate 40 mL/min and UV detection at 220 nm. (S)-N-(1-(4-fluoro-3-isopropoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-5-methyl-4-(trifluoromethyl)thiazol-2-amine eluted at a retention time of 10.99 min (13 mg, 77% yield). LCMS: RT=4.38 min [M+H] 649.2 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm). NMR: 400 MHz 1H (CDCl3) 7.18 ppm, 1H, m; 7.11 ppm, 3H, m; 6.97 ppm, 5H, m; 6.59 ppm, 2H, d, J=7.07 Hz; 5.86 ppm, 1H, m; 4.46 ppm, 1H, m; 3.71 ppm, 2H, s; 2.29 ppm, 3H, m; 1.24 ppm, 6H, dd, J=8.84, 6.06 Hz.

Workup

  1. customThe reaction vessel was sealed
  2. customThe solid was removed by filtration
  3. customthe filtrate was purified by preparative HPLC Phenomenex AXIA Luna
  4. wait30×75 mm Ballistic column 50-100% ACN (90% in water, 0.1% TFA) gradient over 10 min with flow rate 40 mL/min and UV detection at 220 nm
  5. wash(S)-N-(1-(4-fluoro-3-isopropoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-5-methyl-4-(trifluoromethyl)thiazol-2-amine eluted at a retention time of 10.99 min (13 mg, 77% yield)
  6. washLCMS: RT=4.38 min [M+H] 649.2 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm)

Sources & evidence

ORD record
ord-058ff1a13f1d4aae8077c9e816c61998
Source dataset
uspto-grants-2010_01
Patent number
US07652023B2

Reaction notes

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