4-Methylmorpholine → HCID 53495244, compound

HRID 77161Notes

Reaction equation

HRID 77161 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 24906336HCID 24906336, 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 53495244HCID 53495244, compoundYield 59.6%

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, 40 mg, 0.093 mmol) and (R)-2-aminopropanenitrile (Int-X, 13.00 mg, 0.185 mmol) were dissolved in DMF (1 mL). 4-Methylmorpholine (37.5 mg, 0.371 mmol) and HATU (45.8 mg, 0.121 mmol) were added. After stirring 1 h, the mixture was purified by prep HPLC (PHENOMENEX® Luna 5u 21.2×250 mm, gradient elution with Method 2—CH3CN/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 35 min, 20 mL/min, 220 nM, product retention=28.5 min) to provide single enantiomer N-((R)-1-cyanoethyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (27 mg, 0.055 mmol, 59.6% yield): [M+H]+=484.0; 1H NMR (400 MHz, methanol-d4) δ ppm 8.93 (1 H, d, J=7.70 Hz), 8.13-8.24 (2 H, m), 7.50-7.80 (7 H, m), 5.17 (1 H, s), 4.86-4.91 (1 H, m), 1.56 (3 H, d, J=7.04 Hz); HPLC peak RT=9.9 min (Method A).

Workup

  1. customthe mixture was purified by prep HPLC (PHENOMENEX® Luna 5u 21.2×250 mm, gradient elution with Method 2—CH3CN/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 35 min, 20 mL/min, 220 nM, product retention=28.5 min)

Sources & evidence

ORD record
ord-327c9660f2fe45309ea657f55fce6a0f
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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