Trifluoroacetic acid → HCID 67265250, compound

HRID 521606Notes

Reaction equation

HRID 521606 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][C:4]=1[CH3:12].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.C(OC(=O)[NH:50][CH2:51][CH2:52][O:53][C:54]1[CH:59]=[CH:58][C:57]([NH2:60])=[CH:56][C:55]=1[C:61]1[N:62]([CH3:67])[N:63]=[CH:64][C:65]=1[Cl:66])(C)(C)C.[C:69]([OH:75])([C:71]([F:74])([F:73])[F:72])=[O:70]>C(Cl)Cl>[F:72][C:71]([F:74])([F:73])[C:69]([OH:75])=[O:70].[NH2:50][CH2:51][CH2:52][O:53][C:54]1[CH:59]=[CH:58][C:57]([NH:60][C:7](=[O:9])[C:6]2[CH:10]=[CH:11][C:3]([O:2][CH3:1])=[C:4]([CH3:12])[CH:5]=2)=[CH:56][C:55]=1[C:61]1[N:62]([CH3:67])[N:63]=[CH:64][C:65]=1[Cl:66]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 27595834-Methoxy-3-methylbenzoic AcidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67265237HCID 67265237, compound

Product 1

HCID 67265250HCID 67265250, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 4-methoxy-3-methylbenzoic acid (10 mg, 59 HATU (23 mg, 1.1 eq), and Et3N (11 mg, 1.5 eq.) in DCM (1 mL) was stirred 20 min at 40° C. {2-[4-Amino-2-(4-chloro-2-methyl-2H-pyrazol-3-yl)-phenoxy]-ethyl}-carbamic acid tert-butyl ester (18 mg, 50 μmol) was added into the acid-HATU solution, and the reaction was stirred overnight at 40 C. The reaction was treated with TFA (˜0.2 mL) and heated to 90° C. for 1 h. The reaction was filtered through a strong cation exchage resin to remove impurity, TFA, and tetramethyl urea, and purified by prep-HPLC: Waters YMC ODS-A™ C18 column (5μ, 4.6×50 mm), 5% v/v CH3CN (containing 0.05% v/v TFA) in H2O (containing 0.05% v/v TFA) gradient to 60% v/v CH3CN in H2O, 20 mL/min. N-[4-(2-Amino-ethoxy)-3-(4-chloro-2-methyl-2H-pyrazol-3-yl)-phenyl]-4-methoxy-3-methyl-benzamide trifluoroacetate (14 mg, 69%) was obtained as a white powder. LCMS m/z (%)=415.3 (M+H 35Cl, 100), 417.3 (M+H 37Cl, 31). 1H NMR (400 MHz, DMSO-d6) δ: 10.1 (s, 1H), 7.93 (dd, J=2.5 and 8.8 Hz, 1H), 7.91-7.82 (m, 4H), 7.79 (bs, 1H), 7.70 (d, J=2.5 Hz, 1H), 7.65 (s, 1H), 7.27 (d, J=9.0 Hz, 1H), 7.06 (d, J=8.8 Hz, 1H), 4.19 (m, 2H), 3.86 (s, 3H), 3.67 (s, 3H), 3.16 (m, 2H), 2.21 (s, 3H).

Workup

  1. filtrationThe reaction was filtered through a strong cation exchage resin
  2. customto remove impurity, TFA, and tetramethyl urea
  3. custompurified by prep-HPLC: Waters YMC ODS-A™ C18 column (5μ, 4.6×50 mm), 5% v/v CH3CN (
  4. additioncontaining 0.05% v/v TFA) in H2O (
  5. additioncontaining 0.05% v/v TFA) gradient to 60% v/v CH3CN in H2O, 20 mL/min

Sources & evidence

ORD record
ord-b8153643322e4a528fd9938da8827c18
Source dataset
uspto-grants-2016_05
Patent number
US09328107B2

Reaction notes

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