4-Methylmorpholine → HCID 53495246, compound

HRID 77164Notes

Reaction equation

HRID 77164 reaction equation
[OH:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:16]=[C:15]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:18]=3[C:28]([F:31])([F:30])[F:29])[O:14][N:13]=2)=[CH:8][CH:7]=1)[C:3](O)=[O:4].C[N:33]1[CH2:38][CH2:37][O:36]CC1.CN([C:42]([O:46]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[OH:36][CH2:37][CH:38]([NH:33][C:3](=[O:4])[CH:2]([OH:1])[C:6]1[CH:7]=[CH:8][C:9]([C:12]2[N:16]=[C:15]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:18]=3[C:28]([F:30])([F:31])[F:29])[O:14][N:13]=2)=[CH:10][CH:11]=1)[CH2:42][OH:46]

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 674589572-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid

Product 1

HCID 53495246HCID 53495246, compoundYield 32.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Single enantiomer 2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-Va, 30 mg, 0.070 mmol), (R/S)-2-aminopropane-1,3-diol (9.51 mg, 0.104 mmol), 4-methylmorpholine (28.1 mg, 0.278 mmol), and HATU (34.4 mg, 0.090 mmol) were dissolved in DMF (1 mL). After stirring 1 h, the reaction mixture was purified by prep HPLC (PHENOMENEX® Luna 5u 21.2×100 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=11.33 min) to provide the product N-(1,3-dihydroxypropan-2-yl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide as a mixture of diastereomers (13 mg, 0.023 mmol, 32.6% yield): LCMS=505.1 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.12-8.27 (2 H, m), 7.92-8.01 (1 H, m), 7.50-7.81 (7 H, m), 5.16 (1 H, s), 3.95 (1 H, dt, J=8.53, 5.42 Hz), 3.55-3.79 (4 H, m); HPLC peak RT=8.3 min (Method A).

Workup

  1. customthe reaction mixture was purified by prep HPLC (PHENOMENEX® Luna 5u 21.2×100 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=11.33 min)

Sources & evidence

ORD record
ord-377e5ebd045e4222b28701ef0d20efb7
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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