Dimethylformamide → Trifluoroacetic acid

HRID 77230Notes

Reaction equation

HRID 77230 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].[CH3:32][N:33]1[C:37]([CH2:38][NH2:39])=[CH:36][C:35]([CH3:40])=[N:34]1.CN1CC[O:45]CC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN([CH:75]=[O:76])C>>[CH3:32][N:33]1[C:37]([CH2:38][NH:39][C:3](=[O:4])[CH:2]([OH:1])[C:6]2[CH:7]=[CH:8][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:31])([F:30])[F:29])[O:14][N:13]=3)=[CH:10][CH:11]=2)=[CH:36][C:35]([CH3:40])=[N:34]1.[C:75]([OH:76])([C:28]([F:31])([F:30])[F:29])=[O:45]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 1257670(1,3-Dimethyl-1H-pyrazol-5-yl)methanamineHCID 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 2

HCID 6422Trifluoroacetic acidYield 25.9%HCID 68232703HCID 68232703, compound

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, 17 mg, 0.039 mmol), (1,3-dimethyl-1H-pyrazol-5-yl)methanamine (7.40 mg, 0.059 mmol), 4-methylmorpholine (15.95 mg, 0.158 mmol), and HATU (19.48 mg, 0.051 mmol) were dissolved in 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=13.0 min) to provide (R/S)-N-((1,3-dimethyl-1H-pyrazol-5-yl)methyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide, TFA (7 mg, 10.22 μmol, 25.9% yield): LCMS=539.3 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.11-8.23 (2 H, m), 7.52-7.76 (7 H, m), 6.06 (1 H, s), 5.18 (1 H, s), 4.44 (2 H, s), 3.77 (3 H, s), 2.21 (3 H, s); HPLC peak RT=9.0 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=13.0 min)

Sources & evidence

ORD record
ord-6e19dbce6c784ba1aaafb9b7efb4fa74
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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