1,2-Dichloroethane → 4-(3-amino-6-((1R,3R)-3-hydroxycyclopentyl)pyrazin-2-yl)-2-fluoro-N-((S)-1-(3-fluoro-5-iodophenyl)-2-hydroxyethyl)benzamide

HRID 596118Notes

Reaction equation

HRID 596118 reaction equation
[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[C:16]([F:23])[CH:15]=2)=[N:4][C:5]([C@@H:8]2[CH2:12][CH2:11][C@@H:10]([OH:13])[CH2:9]2)=[CH:6][N:7]=1.[NH2:24][C@@H:25]([C:28]1[CH:33]=[C:32]([I:34])[CH:31]=[C:30]([F:35])[CH:29]=1)[CH2:26][OH:27].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH:24][C@@H:25]([C:28]3[CH:33]=[C:32]([I:34])[CH:31]=[C:30]([F:35])[CH:29]=3)[CH2:26][OH:27])=[O:20])=[C:16]([F:23])[CH:15]=2)=[N:4][C:5]([C@@H:8]2[CH2:12][CH2:11][C@@H:10]([OH:13])[CH2:9]2)=[CH:6][N:7]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 118045250(S)-2-amino-2-(3-fluoro-5-iodophenyl)ethanolHCID 1180462134-(3-amino-6-((1R,3R)-3-hydroxycyclopentyl)pyrazin-2-yl)-2-fluorobenzoic acid

Product 1

HCID 1180460514-(3-amino-6-((1R,3R)-3-hydroxycyclopentyl)pyrazin-2-yl)-2-fluoro-N-((S)-1-(3-fluoro-5-iodophenyl)-2-hydroxyethyl)benzamideYield 45.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (4-(3-amino-6-((1R,3R)-3-hydroxycyclopentyl)pyrazin-2-yl)-2-fluorobenzoic acid) (6 mg, 0.019 mmol), (S)-2-amino-2-(3-fluoro-5-iodophenyl)ethanol (8.96 mg, 0.028 mmol), HOAt (5.15 mg, 0.038 mmol) and EDC (7.25 mg, 0.038 mmol) in DMF (1 ml) was added DIEA (0.036 ml, 0.208 mmol). The resultant mixture was stirred over night at RT. The mixture was diluted with EtOAc, washed with water three times and brine, dried with Na2SO4, filtered and concentrated to afford the crude product as a light yellow viscous liquid. This crude was purified by prep HPLC to afford desired product (6 mg, 45.2% yield) as a light yellow solid, a TFA salt. LC-MS: (MH+) 581.0 at 0.726 min. 1H NMR (400 MHz, CD3CN) δ ppm 1.56-1.82 (m, 2H) 2.01-2.30 (m, 3H) 3.47 (t, J=8.61 Hz, 1H) 3.73-3.92 (m, 3H) 4.32-4.45 (m, 2H) 5.05-5.19 (m, 1H) 7.16-7.27 (m, 1H) 7.48 (dt, J=8.12, 1.81 Hz, 1H) 7.56-7.71 (m, 4H) 7.74-7.81 (m, 1H) 7.97 (t, J=7.83 Hz, 1H).

Workup

  1. washwashed with water three times and brine
  2. dry with materialdried with Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto afford the crude product as a light yellow viscous liquid
  6. customThis crude was purified by prep HPLC

Sources & evidence

ORD record
ord-ad9199e482294b28918fa9262cf14f92
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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