Diisopropylethylamine → HCID 68408480, compound

HRID 2066837Notes

Reaction equation

HRID 2066837 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:21]([CH3:23])[CH3:22])[C:6]2[O:10][C:9]([C:11]3[CH:19]=[CH:18][C:14]([C:15](O)=[O:16])=[CH:13][CH:12]=3)=[N:8][C:7]=2[CH:20]=1)#[N:2].CN(C(ON1N=NC2C1=CC=CC=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[NH2:68][CH2:69][C@H:70]1[O:74][C:73](=[O:75])[NH:72][C@@H:71]1[C:76]1[CH:81]=[CH:80][C:79]([F:82])=[C:78]([F:83])[CH:77]=1>ClCCl.C(=O)(O)[O-].[Na+]>[C:1]([C:3]1[CH:4]=[C:5]([CH:21]([CH3:22])[CH3:23])[C:6]2[O:10][C:9]([C:11]3[CH:19]=[CH:18][C:14]([C:15]([NH:68][CH2:69][C@H:70]4[O:74][C:73](=[O:75])[NH:72][C@@H:71]4[C:76]4[CH:81]=[CH:80][C:79]([F:82])=[C:78]([F:83])[CH:77]=4)=[O:16])=[CH:13][CH:12]=3)=[N:8][C:7]=2[CH:20]=1)#[N:2]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27960291-Hydroxybenzotriazole hydrateHCID 573699454-(5-Cyano-7-isopropylbenzo[d]oxazol-2-yl)benzoic acid2×HCID 68409788HCID 68409788, compound

Product 1

HCID 68408480HCID 68408480, compoundYield 45.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 516892Sodium BicarbonateSolvent

Procedure

A suspension of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoic acid (INTERMEDIATE 2, 67 mg, 0.219 mmol), o-benzotriazol-1-yl-tetramethyluronium hexafluorophosphate (166 mg, 0.438 mmol), 1-hydroxybenzotriazole hydrate (50 mg, 0.327 mmol), and diisopropylethylamine (0.2 ml, 1.145 mmol) in dichloromethane (1 ml) was stirred for 5 min at room temperature, and then a solution of (4R,5R)-5-(aminomethyl)-4-(3,4-difluorophenyl)-1,3-oxazolidin-2-one in dichloromethane (1 ml) was added. The mixture was stirred overnight at 25° C. The mixture was diluted with 10 ml of saturated sodium bicarbonate solution and 10 ml of dichloromethane. The phases were separated and the aqueous phase was extracted with 2×10 ml of dichloromethane. The combined organics were washed with 10 ml of brine, dried (sodium sulfate), and concentrated. The residue was purified by flash chromatography on a Biotage Horizon, 25M column, eluting with 1 column volume of 100% dichloromethane followed by a gradient of 0 to 100% ethyl acetate in dichloromethane over 10 column volumes, to provide the title compound (51 mg, 0.099 mmol, 45.1% yield). Mass spectrum (ESI) 517.2 (M+2). 1H NMR (500 MHz, CDCl3): δ 8.36 (d, J=8.5 Hz, 2H), 8.05 (d, J=8.5 Hz, 2H), 7.95 (s, 1H), 7.52 (s, 1H), 7.35 (m, 1H), 7.23 (m, 2H), 6.02 (s, 1H), 4.79 (d, J=7.5 Hz, 1H), 4.48 (m, 1H), 3.05 (m, 1H), 3.83 (m, 1H), 3.49 (m, 2H), 1.47 (d, J=7.0 Hz, 6H).

Workup

  1. stirringThe mixture was stirred overnight at 25° C
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with 2×10 ml of dichloromethane
  4. washThe combined organics were washed with 10 ml of brine
  5. dry with materialdried (sodium sulfate)
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography on a Biotage Horizon, 25M column
  8. washeluting with 1 column volume of 100% dichloromethane

Sources & evidence

ORD record
ord-db47be8ea8ac452aadf4ae29bc434531
Source dataset
uspto-grants-2012_10
Patent number
US08293721B2

Reaction notes

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