4-Methylmorpholine → HCID 53496091, compound

HRID 77192Notes

Reaction equation

HRID 77192 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[C:21]([C:22]([F:25])([F:24])[F:23])=[C:20]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[O:19][N:18]=3)[O:14][N:13]=2)=[CH:8][CH:7]=1)[C:3](O)=[O:4].Cl.[CH2:33]([NH2:35])[CH3:34].C[N:37]1CC[O:40][CH2:39][CH2:38]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:33]([NH:35][C:39](=[O:40])[CH2:38][NH:37][C:3](=[O:4])[CH:2]([OH:1])[C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:16]=[C:15]([C:17]3[C:21]([C:22]([F:25])([F:23])[F:24])=[C:20]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[O:19][N:18]=3)[O:14][N:13]=2)=[CH:8][CH:7]=1)[CH3:34]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 11198Ethylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67458660(R/S)-2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid

Product 1

HCID 53496091HCID 53496091, compoundYield 15.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(R/S)-2-Hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-IX, 24 mg, 0.049 mmol), ethanamine-HCl (6.01 mg, 0.074 mmol), 4-methylmorpholine (19.88 mg, 0.197 mmol), and HATU (24.29 mg, 0.064 mmol) were added to DMF (1 mL). This was stirred for 1 h before it 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 15 min, 20 mL/min, 220 nM, product retention=15.7 min) to provide (R/S)-N-(2-(ethylamino)-2-oxoethyl)-2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (5 mg, 7.62 μmol, 15.52% yield): LCMS=516.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.17 (2 H, d, J=8.36 Hz), 7.59-7.84 (7 H, m), 5.20 (1 H, s), 3.79-3.99 (2 H, m), 3.15-3.27 (2 H, m), 1.11 (3 H, t, J=7.26 Hz); HPLC peak RT=8.6 min (Method A).

Workup

  1. customwas 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 15 min, 20 mL/min, 220 nM, product retention=15.7 min)

Sources & evidence

ORD record
ord-0ffe5008b7f44f0081d66278995cc2d0
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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