4-Methylmorpholine → HCID 53496466, compound

HRID 77213Notes

Reaction equation

HRID 77213 reaction equation
[OH:1][CH:2]([C:11]1[CH:16]=[CH:15][C:14]([C:17]2[N:21]=[C:20]([C:22]3[O:26][N:25]=[C:24]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[C:23]=3[C:33]([F:36])([F:35])[F:34])[O:19][N:18]=2)=[CH:13][CH:12]=1)[C:3]([NH:5][CH2:6][CH2:7][C:8](O)=[O:9])=[O:4].C[N:38]1[CH2:43][CH2:42][O:41]C[CH2:39]1.[CH3:44]N(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[OH:1][CH:2]([C:11]1[CH:16]=[CH:15][C:14]([C:17]2[N:21]=[C:20]([C:22]3[O:26][N:25]=[C:24]([C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)[C:23]=3[C:33]([F:36])([F:34])[F:35])[O:19][N:18]=2)=[CH:13][CH:12]=1)[C:3]([NH:5][CH2:6][CH2:7][C:8]([N:38]1[CH2:43][C:42]([OH:41])([CH3:44])[CH2:39]1)=[O:9])=[O:4]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 534964603-(2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamido)propanoic acid

Product 1

HCID 53496466HCID 53496466, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(R/S)-3-(2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamido)propanoic acid (Int-V, 25 mg, 0.050 mmol), 4-methylmorpholine (20.13 mg, 0.199 mmol), 3-methylazetidin-3-ol, HCl (6.15 mg, 0.050 mmol), and HATU (24.60 mg, 0.065 mmol) were added to DMF (1 mL). This was stirred for 1 h before it was purified by prep HPLC (Sun Fire C18 5u19×100 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 10 min, 20 mL/min, 220 nM, product retention=11.3 min) to provide (R/S)-2-hydroxy-N-(3-(3-hydroxy-3-methylazetidin-1-yl)-3-oxopropyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (9 mg, 0.014 mmol, 27.8% yield): LCMS=572.3 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.16-8.20 (2 H, m), 7.54-7.74 (7 H, m), 5.11 (1 H, s), 3.96-4.04 (2 H, m), 3.81-3.87 (2 H, m), 3.47-3.52 (2 H, m), 2.36-2.43 (2 H, m), 1.44 (3 H, d, J=6.60 Hz); HPLC peak RT=8.3 min (Method A).

Workup

  1. customwas purified by prep HPLC (Sun Fire C18 5u19×100 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 10 min, 20 mL/min, 220 nM, product retention=11.3 min)

Sources & evidence

ORD record
ord-23cefe14a3824e2ea18091bbe2a7758e
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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