Dimethylformamide → Trifluoroacetic acid

HRID 77195Notes

Reaction equation

HRID 77195 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].[NH2:32][CH2:33][C:34]1[N:35]=[C:36]([NH2:39])[S:37][CH:38]=1.CN1CC[O:44]CC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN([CH:74]=[O:75])C>>[NH2:39][C:36]1[S:37][CH:38]=[C:34]([CH2:33][NH:32][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:23]=[CH:24][CH:25]=[CH:26][CH:27]=5)[C:18]=4[C:28]([F:29])([F:30])[F:31])[O:14][N:13]=3)=[CH:8][CH:7]=2)[N:35]=1.[C:74]([OH:75])([C:28]([F:31])([F:30])[F:29])=[O:44]

Participants

7

Reactant 5

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 224015214-(Aminomethyl)-1,3-thiazol-2-amineHCID 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 17.4%HCID 53496093HCID 53496093, 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, 30 mg, 0.070 mmol), 4-(aminomethyl)thiazol-2-amine (13.48 mg, 0.104 mmol), 4-methylmorpholine (28.1 mg, 0.278 mmol), and HATU (34.4 mg, 0.090 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=11.4 min) to provide (R/S)-N-((2-aminothiazol-4-yl)methyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide, TFA (10 mg, 0.012 mmol, 17.4% yield): LCMS=543.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.18 (2 H, d, J=8.36 Hz), 7.53-7.78 (7 H, m), 6.54 (1 H, s), 5.21 (1 H, s), 4.32(2 H, s); HPLC peak RT=8.1 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=11.4 min)

Sources & evidence

ORD record
ord-563b03dd3c9244afa4da4904bac157cf
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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