Dimethylformamide → HCID 53496737, compound

HRID 77227Notes

Reaction equation

HRID 77227 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].C[N:33]1[CH2:38][CH2:37]OCC1.CN(C(ON1N=N[C:49]2[CH:50]=[CH:51][CH:52]=N[C:48]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:63][N:64](C=O)C>>[C:63]([CH:38]([C:37]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[NH:33][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[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)#[N:64]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 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 53496737HCID 53496737, compoundYield 27.2%

Procedure

2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-Va, 20 mg, 0.046 mmol), (R/S)-2-phenylglycinonitrile hydrochloride (11.73 mg, 0.070 mmol), 4-methylmorpholine (18.76 mg, 0.185 mmol), and HATU (22.92 mg, 0.060 mmol) were added to DMF (2 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 10 min, product retention=12.2 min (20 mL/min, 220 nM) to provide N-(cyano(phenyl)methyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (8 mg, 0.013 mmol, 27.2% yield) as a mixture of diastereomers. LCMS=546.3 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.17 (2 H, dd, J=8.36, 6.38 Hz), 7.32-7.77 (12 H, m), 6.18 (1 H, d, J=7.04 Hz), 5.24 (1 H, d, J=8.14 Hz); HPLC peak RT=10.9 min (Method A).

Workup

  1. customwas purified by prep HPLC (
  2. washPHENOMENEX® Luna 5u 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-d5d979970fdb4ae7abcdf332761e060f
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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