N-Benzyloxycarbonyl-beta-alanine → HCID 90985399, compound

HRID 2093598Notes

Reaction equation

HRID 2093598 reaction equation
[C:1]([NH:11][CH2:12][CH2:13][C:14]([OH:16])=O)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].CN(C(ON1N=NC2C1=CC=CC=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[C:60]([C:62]1[CH:63]=[C:64]([CH:87]([CH3:89])[CH3:88])[C:65]2[O:69][C:68]([C:70]3[CH:85]=[CH:84][C:73]([C:74]([NH:76][CH2:77][CH:78]4[CH2:83][CH2:82][NH:81][CH2:80][CH2:79]4)=[O:75])=[CH:72][CH:71]=3)=[N:67][C:66]=2[CH:86]=1)#[N:61]>ClCCl.C(=O)(O)[O-].[Na+]>[C:60]([C:62]1[CH:63]=[C:64]([CH:87]([CH3:89])[CH3:88])[C:65]2[O:69][C:68]([C:70]3[CH:71]=[CH:72][C:73]([C:74]([NH:76][CH2:77][CH:78]4[CH2:83][CH2:82][N:81]([C:14](=[O:16])[CH2:13][CH2:12][NH:11][C:1](=[O:2])[O:3][CH2:4][C:5]5[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=5)[CH2:80][CH2:79]4)=[O:75])=[CH:84][CH:85]=3)=[N:67][C:66]=2[CH:86]=1)#[N:61]

Participants

8

Reactant 5

HCID 75313N-Benzyloxycarbonyl-beta-alanineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68745687HCID 68745687, compound2×

Product 1

HCID 90985399HCID 90985399, compoundYield 54.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
25 °C

Procedure

To a suspension of N-carbobenzoxy-β-alanine (20 mg, 0.090 mmol) in dichloromethane (2 ml) were added o-benzotriazol-1-yl-tetramethyluronium hexafluorophosphate (65 mg, 0.171 mmol), 1-hydroxybenzotriazole (15 mg, 0.111 mmol), and diisopropylethylamine (0.040 ml, 0.229 mmol). After 5 min, 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-(piperidin-4-ylmethyl)benzamide (30 mg, 0.075 mmol, INTERMEDIATE 15) was added and the mixture was stirred overnight at 25° C. The mixture was diluted with saturated sodium bicarbonate solution (10 ml) and dichloromethane (10 ml). The phases were separated and the aqueous phase was extracted with dichloromethane (2×10 ml). 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, 25S column, eluting with 1 column volume of 100% dichloromethane followed by a gradient of 0 to 50% methanol in dichloromethane over 10 column volumes. The resulting mixture was repurified by preparative thin-layer chromatography, eluting with 5% methanol in dichloromethane provide the title compound (24.8 mg, 0.041 mmol, 54.8% yield). Mass spectrum (ESI) 630.1 (M+1).

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase was extracted with dichloromethane (2×10 ml)
  3. washThe combined organics were washed with 10 ml of brine
  4. dry with materialdried (sodium sulfate)
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on a Biotage Horizon, 25S column
  7. washeluting with 1 column volume of 100% dichloromethane
  8. customThe resulting mixture was repurified by preparative thin-layer chromatography
  9. washeluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-295549e0ed37408d91c2c13d769b8957
Source dataset
uspto-grants-2013_05
Patent number
US08445480B2

Reaction notes

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