Diisopropylethylamine → 4-{[(4-Chloro-benzenesulfonyl)-((R)-5,5-difluoro-2-oxo-azepan-3-yl)-amino]-methyl}-3-fluoro-N-pyrrolidin-1-yl-benzamide

HRID 1783400Notes

Reaction equation

HRID 1783400 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:22][C:23]2[CH:31]=[CH:30][C:26]([C:27]([OH:29])=O)=[CH:25][C:24]=2[F:32])[C@@H:12]2[CH2:18][C:17]([F:20])([F:19])[CH2:16][CH2:15][NH:14][C:13]2=[O:21])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[B-](F)(F)(F)F.CN(C(ON1C(=O)C=CC=C1)=[N+](C)C)C.CCN(C(C)C)C(C)C.Cl.[NH2:63][N:64]1[CH2:68][CH2:67][CH2:66][CH2:65]1>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:22][C:23]2[CH:31]=[CH:30][C:26]([C:27]([NH:63][N:64]3[CH2:68][CH2:67][CH2:66][CH2:65]3)=[O:29])=[CH:25][C:24]=2[F:32])[C@@H:12]2[CH2:18][C:17]([F:20])([F:19])[CH2:16][CH2:15][NH:14][C:13]2=[O:21])(=[O:9])=[O:10])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 2733204O-(2-Oxo-1(2H)-pyridyl)-N,N,N',N'-tetramethyluronium TetrafluoroborateHCID 3017392Pyrrolidin-1-amine monohydrochlorideHCID 686243374-{[(4-Chloro-benzenesulfonyl)-((R)-5,5-difluoro-2-oxo-azepan-3-yl)-amino]-methyl}-3-fluoro-benzoic acid

Product 1

HCID 160354754-{[(4-Chloro-benzenesulfonyl)-((R)-5,5-difluoro-2-oxo-azepan-3-yl)-amino]-methyl}-3-fluoro-N-pyrrolidin-1-yl-benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-{[(4-Chloro-benzenesulfonyl)-((R)-5,5-difluoro-2-oxo-azepan-3-yl)-amino]-methyl}-3-fluoro-benzoic acid (50 mg, 0.10 mmol) was dissolved in DMF (1 ml) and activated with the coupling reagent TPTU (33 mg, 0.11 mmol) and Hünig's base (0.03 ml, 0.26 mmol) for 2 min. 1-Aminopyrrolidine hydrochloride (0.013 g, 0.22 mmol) and further Hünig's base (0.03 ml, 0.26 mmol were added. After 1 h the reaction mixture was concentrated under reduced pressure and the residue taken up in ethyl acetate and washed with 5% KHSO4/10% K2SO4 (2×), water, brine, dried (MgSO4), filtered, concentrated under reduced pressure and purified over silica gel (ethyl acetate->ethyl acetate/5% MeOH) and the purified product was lyophilized: white lyophilisate 32 mg;

Workup

  1. concentrationAfter 1 h the reaction mixture was concentrated under reduced pressure
  2. washwashed with 5% KHSO4/10% K2SO4 (2×), water, brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. custompurified over silica gel (ethyl acetate->ethyl acetate/5% MeOH)

Sources & evidence

ORD record
ord-903a00b6940a4f14a328e8c3828555f4
Source dataset
uspto-grants-2009_03
Patent number
US07501406B2

Reaction notes

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