4-Methylmorpholine → HCID 53496225, compound

HRID 77215Notes

Reaction equation

HRID 77215 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].Cl.Cl.[NH2:34][CH2:35][C:36]1[C:37]([NH2:43])=[N:38][C:39]([CH3:42])=[N:40][CH:41]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CO.CN(C=O)C>[NH2:43][C:37]1[C:36]([CH2:35][NH:34][C:3](=[O:4])[CH:2]([OH:1])[C:6]2[CH:11]=[CH:10][C:9]([C:12]3[N:16]=[C:15]([C:17]4[O:21][N:20]=[C:19]([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=5)[C:18]=4[C:28]([F:29])([F:30])[F:31])[O:14][N:13]=3)=[CH:8][CH:7]=2)=[CH:41][N:40]=[C:39]([CH3:42])[N:38]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 715845-Aminomethyl-2-methylpyrimidin-4-ylamine dihydrochlorideHCID 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 53496225HCID 53496225, compoundYield 67.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 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, 50 mg, 0.116 mmol), 5-(aminomethyl)-2-methylpyrimidin-4-amine-2 HCl (36.7 mg, 0.174 mmol), 4-methylmorpholine (46.9 mg, 0.464 mmol), and HATU (57.3 mg, 0.151 mmol) were added to DMF (2 mL). The mixture was stirred for 1 h. Methanol was added and the mixture was filtered for prep HPLC. 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 10 min, 20 mL/min, 220 nM, product retention=11.2 min) to provide single enantiomer N-((4-amino-2-methylpyrimidin-5-yl)methyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (45 mg, 0.078 mmol, 67.6% yield): LCMS=552.3 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.13-8.25 (2 H, m), 7.91 (1 H, s), 7.53-7.75 (7 H, m), 5.21 (1 H, s), 4.20-4.39 (2 H, m), 2.51 (3 H, s); HPLC peak RT=8.3 min (Method A).

Workup

  1. filtrationthe mixture was filtered for prep HPLC
  2. customIt 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 10 min, 20 mL/min, 220 nM, product retention=11.2 min)

Sources & evidence

ORD record
ord-8067d47e8be7493daad7e4b5e80196cd
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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