4-Methylmorpholine → HCID 53495394, compound

HRID 77171Notes

Reaction equation

HRID 77171 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]([OH:5])=O.[NH2:32][CH2:33][CH2:34][CH2:35][OH:36].CN1CCOCC1.CN(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: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:29])([F:30])[F:31])[O:14][N:13]=2)=[CH:8][CH:7]=1)[C:3]([NH:32][CH2:33][CH2:34][CH2:35][OH:36])=[O:5]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 90863-Amino-1-propanolHCID 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 53495394HCID 53495394, compoundYield 26.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(R/S)-2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-V, 30 mg, 0.070 mmol), 3-aminopropan-1-ol (7.84 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). The mixture was stirred for 1 h and then purified by prep HPLC (PHENOMENEX® Luna 5u 21×250 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 30 min, 25 mL/min, 220 nM, product retention=29.4 min) to provide (R/S)-2-hydroxy-N-(3-hydroxypropyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (12 mg, 0.018 mmol, 26.5% yield): LCMS=489.1 [M+H]+; 1H NMR (400 MHz, chloroform-d) δ ppm 8.12-8.30 (2 H, m), 7.47-7.74 (7 H, m), 7.06 (1 H, br. s.), 5.22 (1 H, d, J=4.83 Hz), 4.38 (1 H, t, J=5.71 Hz), 3.56-3.75 (2 H, m), 3.31-3.52 (2 H, m), 1.91-2.08 (1 H, m), 1.63-1.81 (2 H, m); HPLC peak RT=8.4 min (Method A).

Workup

  1. custompurified by prep HPLC (PHENOMENEX® Luna 5u 21×250 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 30 min, 25 mL/min, 220 nM, product retention=29.4 min)

Sources & evidence

ORD record
ord-0e521cbae03b4a3dbb0c7ef66f04aa34
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

Loading…