Diisopropylethylamine → (1R,2R)-N-(tert-butoxy)-1-fluoro-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxamide

HRID 736815Notes

Reaction equation

HRID 736815 reaction equation
[F:1][C@:2]1([C:30]([OH:32])=O)[CH2:6][CH2:5][CH2:4][C@H:3]1[NH:7][S:8]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:22]=[C:21]([CH3:29])[CH:20]=2)=[CH:13][CH:12]=1)(=[O:10])=[O:9].F[P-](F)(F)(F)(F)F.[N:40]1([O:49][P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.Cl.[C:61](NO)([CH3:64])([CH3:63])[CH3:62].C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[C:61]([O:49][NH:40][C:30]([C@@:2]1([F:1])[CH2:6][CH2:5][CH2:4][C@H:3]1[NH:7][S:8]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:22]=[C:21]([CH3:29])[CH:20]=2)=[CH:13][CH:12]=1)(=[O:9])=[O:10])=[O:32])([CH3:62])([CH3:63])[CH3:64]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 2777896N-tert-butylhydroxylamine hydrochlorideHCID 68819242(1R,2R)-1-fluoro-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxylic acid

Product 1

HCID 86607911(1R,2R)-N-(tert-butoxy)-1-fluoro-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxamideYield 73.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 0.15 g (3 mmol) of (1R,2R)-1-fluoro-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxylic acid in DMF (4 mL) was added benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate (0.16 g, 1.2 eq), tert-butyl hydroxylamine hydrochloride (0.078 g, 2 eq) and diisopropylethylamine (0.22 mL, 4 eq). The resulting reaction mixture was stirred for 18 h, and then taken up in ethyl acetate, washed with brine, dried over Mg2SO4, filtered and concentrated. The residue was purified using silica chromatography, eluting with a gradient of 50-80% ethyl acetate/hexanes to afford (1R,2R)-N-(tert-butoxy)-1-fluoro-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxamide (0.14 g, 60%, 2 steps). MS: 530.2 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. washwashed with brine
  3. dry with materialdried over Mg2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified
  7. washeluting with a gradient of 50-80% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-9ae6c459ef584a0b92e88d69dd3f22a3
Source dataset
uspto-grants-2009_09
Patent number
US07595327B2

Reaction notes

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