Dimethylformamide → HCID 53495943, compound

HRID 77190Notes

Reaction equation

HRID 77190 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]([OH:5])=O.[N:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38][NH2:39])[CH:33]=1.CN(C([O:47]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.CN([CH:74]=[O:75])C>>[OH:1][CH:2]([C:6]1[CH:7]=[CH:8][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:10][CH:11]=1)[C:3]([NH:39][CH2:38][C:34]1[CH:33]=[N:32][CH:37]=[CH:36][CH:35]=1)=[O:5].[C:74]([OH:75])([C:22]([F:25])([F:24])[F:23])=[O:47]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 310183-PyridinemethanamineHCID 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 53495943HCID 53495943, compoundYield 41.8%

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, 30 mg, 0.070 mmol), pyridin-3-ylmethanamine (11.28 mg, 0.104 mmol), HATU (34.4 mg, 0.090 mmol), and 4-methylmorpholine (28.1 mg, 0.278 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 10 min, 20 mL/min, 220 nM, product retention=10.7 min) to provide (R/S)-2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)-N-(pyridin-3-ylmethyl)acetamide-TFA (20 mg, 0.029 mmol, 41.8% yield): LCMS=522.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.72 (2 H, br. s.), 8.47 (1 H, d, J=8.14 Hz), 8.15 (2 H, d, J=8.58 Hz), 7.99 (1 H, dd, J=7.92, 5.94 Hz), 7.57-7.88 (7 H, m), 5.22 (1 H, s), 4.62 (2 H, s); HPLC peak RT=7.7 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 10 min, 20 mL/min, 220 nM, product retention=10.7 min)

Sources & evidence

ORD record
ord-92b0d886364b4c7388b7cfe1683c40df
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

Loading…