Triethylamine → HCID 90411842, compound

HRID 1522040Notes

Reaction equation

HRID 1522040 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:29][CH3:30])=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][C:15]([C:17]4[CH2:23][CH:22]5[N:24]([CH2:25][C:26](O)=[O:27])[CH:19]([CH2:20][CH2:21]5)[CH:18]=4)=[CH:16][C:9]=23)[CH:7]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.[NH:72]1[CH2:75][CH:74]([OH:76])[CH2:73]1>CN(C)C=O.[Cl-].[Na+].O.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:29][CH3:30])=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][C:15]([C:17]4[CH2:23][CH:22]5[N:24]([CH2:25][C:26]([N:72]6[CH2:75][CH:74]([OH:76])[CH2:73]6)=[O:27])[CH:19]([CH2:20][CH2:21]5)[CH:18]=4)=[CH:16][C:9]=23)[CH:7]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 27592903-Hydroxyazetidine hydrochlorideHCID 90411375HCID 90411375, compound

Product 1

HCID 90411842HCID 90411842, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of Example 304A (0.100 g, 0.225 mmol), (benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (0.141 g, 0.270 mmol), triethylamine (0.157 mL, 1.126 mmol), and azetidin-3-ol.hydrochloride (0.030 g, 0.270 mmol) in N,N-dimethylformamide (2.5 mL) was stirred for 3 hours. The mixture was treated with water and brine and extracted with ethyl acetate (twice). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, concentrated, and purified on silica gel using the ISCO Companion flash system eluting with dichloromethane/methanol/ammonium hydroxide (18:1:0.1 to 12:1:0.1) to give the title compound. 1H NMR (500 MHz, Methanol-d4) δ 1.60-1.70 (m, 1H), 1.91-1.99 (m, 1H), 2.06-2.17 (m, 2H), 2.16-2.27 (m, 1H), 2.82-2.91 (m, 1H), 3.26-3.34 (m, 1H), 3.51-3.58 (m, 1H), 3.63-3.70 (m, 1H), 3.76-3.78 (m, 4H), 4.00 (td, J=9.9, 4.3 Hz, 1H), 4.21 (dd, J=10.6, 6.9 Hz, 1H), 4.33-4.46 (m, 1H), 4.49-4.69 (m, 2H), 6.23 (s, 1H), 6.48-6.53 (m, 1H), 7.07 (d, J=5.1 Hz, 1H), 7.09-7.20 (m, 3H), 8.15 (d, J=5.1 Hz, 1H). MS (ESI+) m/z 463.1 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate (twice)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified on silica gel using the ISCO Companion flash system
  7. washeluting with dichloromethane/methanol/ammonium hydroxide (18:1:0.1 to 12:1:0.1)

Sources & evidence

ORD record
ord-f3f86f567b1b4d04984de65a1d667374
Source dataset
uspto-grants-2015_07
Patent number
US09073922B2

Reaction notes

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