4-Methylmorpholine → HCID 53496728, compound

HRID 77137Notes

Reaction equation

HRID 77137 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].CN1CC[O:36]CC1.CN(C(ON1N=[N:54][C:49]2C=[CH:51][CH:52]=[N:53][C:48]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:52]([NH:53][C:48](=[O:36])[CH2:49][NH:54][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)[CH3:51]

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 53496728HCID 53496728, compoundYield 23.6%

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, 0.061 mmol) was dissolved in DMF (1 mL) prior to the addition of 4-methylmorpholine (0.041 mL, 0.369 mmol), ethanamine, HCl (9.02 mg, 0.111 mmol), and HATU (42.0 mg, 0.111 mmol). This was stirred overnight and was then purified by preparative HPLC (PHENOMENEX® Luna 5u C18 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=11.6 min) to give (R/S)-N-(2-(ethylamino)-2-oxoethyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (8.6 mg, 0.014 mmol, 23.60% yield): LCMS=516.2[M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.18 (2 H, d, J=8.36 Hz), 7.65-7.78 (4 H, m), 7.53-7.65 (3 H, m), 5.20 (1 H, s), 3.81-3.96 (2 H, m), 3.23 (2 H, q, J=7.26 Hz), 1.07-1.14 (3 H, m). HPLC Peak RT=9.5 min (Analytical Method D).

Workup

  1. customwas then purified by preparative HPLC (PHENOMENEX® Luna 5u
  2. washC18 21.2×100 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid
  3. customover 10 min

Sources & evidence

ORD record
ord-e19eb3e238cb4bea9d945a279826f762
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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