Diisopropylethylamine → 4-((R)-4-((R)-3-((diethylamino)methyl)morpholino)-4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide

HRID 1476319Notes

Reaction equation

HRID 1476319 reaction equation
[C:1]1([S:7][CH2:8][C@H:9]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([S:21](=[O:24])(=[O:23])[NH2:22])=[CH:17][C:16]=2[S:25]([C:28]([F:31])([F:30])[F:29])(=[O:27])=[O:26])[CH2:10][C:11](O)=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:32]([N:34]([CH2:37][C@@H:38]1[CH2:43][O:42][CH2:41][CH2:40][N:39]1C(OC(C)(C)C)=O)[CH2:35][CH3:36])[CH3:33].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CC(N(C)C)=O.C(OCC)(=O)C>[CH2:32]([N:34]([CH2:37][C@H:38]1[N:39]([C:11](=[O:12])[CH2:10][C@@H:9]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([S:21]([NH2:22])(=[O:23])=[O:24])=[CH:17][C:16]=2[S:25]([C:28]([F:29])([F:31])[F:30])(=[O:27])=[O:26])[CH2:8][S:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:40][CH2:41][O:42][CH2:43]1)[CH2:35][CH3:36])[CH3:33]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66723519(R)-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butanoic acid2×HCID 66723762(R)-tert-butyl 3-((diethylamino)methyl)morpholine-4-carboxylate2×

Product 1

HCID 667235784-((R)-4-((R)-3-((diethylamino)methyl)morpholino)-4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamideYield 30.6%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of (R)-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butanoic acid (INTERMEDIATE 8, 500 mg, 1.00 mmol), (R)—N-ethyl-N-(morpholin-3-ylmethyl)ethanamine hydrochloride salt (INTERMEDIATE 90, 209 mg, 1.00 mmol), DIPEA (0.701 ml, 4.01 mmol) in DMA (5 ml) was added HATU (458 mg, 1.20 mmol). The mixture was stirred for 1 h at room temperature and diluted with ethyl acetate (200 ml). The mixture was washed successively with 1M aq. sodium bisulfate, saturated sodium bicarbonate, and brine. The organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified column chromatography (ISCO, eluting with 0→100% DCM/10% 2 M ammonia in MeOH in DCM over 24 minutes) to give the title product (200 mg, yield: 30.5%).

Workup

  1. washThe mixture was washed successively with 1M aq. sodium bisulfate, saturated sodium bicarbonate, and brine
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe concentrate was purified
  6. washcolumn chromatography (ISCO, eluting with 0→100% DCM/10% 2 M ammonia in MeOH in DCM over 24 minutes)

Sources & evidence

ORD record
ord-5022472939b94f78a6eec096e224d5dc
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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