4-Methylmorpholine → HCID 53472866, compound

HRID 77162Notes

Reaction equation

HRID 77162 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].[NH2:32][C@@H:33]([CH3:36])[C:34]#[N:35].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:34]([C@@H:33]([NH:32][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:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[C:18]=3[C:28]([F:30])([F:31])[F:29])[O:14][N:13]=2)=[CH:10][CH:11]=1)[CH3:36])#[N:35]

Participants

6

Reactant 4

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 12782878HCID 12782878, compoundHCID 674589572-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid

Product 1

HCID 53472866HCID 53472866, compoundYield 27.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-Va, 37 mg, 0.086 mmol), (S)-2-aminopropanenitrile (Int-XI, 9.0 mg, 0.13 mmol) [see also, McLaughlin, M. et al., J. Org. Chem., 68:50-54 (2003)], 4-methylmorpholine (34.7 mg, 0.343 mmol), and HATU (42.4 mg, 0.112 mmol) were dissolved in DMF (1 mL). After stirring 1 h, the reaction mixture was purified by prep HPLC (PHENOMENEX® 21×250 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 38 min, 25 mL/min, 220 nM, product retention=29.3 min) to provide single enantiomer N—((S)-1-cyanoethyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (12 mg, 0.023 mmol, 27.3% yield): [M+H]+=484.2; 1H NMR (400 MHz, methanol-d4) δ ppm 8.13-8.25 (2 H, m), 7.54-7.77 (7 H, m), 5.19 (1 H, s), 4.87 (1 H, q), 1.54 (3 H, d, J=7.04 Hz); HPLC peak RT=11.1 min (Method A).

Workup

  1. customthe reaction mixture was purified by prep HPLC (PHENOMENEX® 21×250 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 38 min, 25 mL/min, 220 nM, product retention=29.3 min)

Sources & evidence

ORD record
ord-2f61f3657f9948f1be2d29f8a7916b2b
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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