Trifluoroacetic acid → Trifluoroacetic acid

HRID 1755222Notes

Reaction equation

HRID 1755222 reaction equation
Cl.Cl.[C:3]1([N:12]2[CH2:16][CH2:15][C@H:14]([NH2:17])[CH2:13]2)[C:4]2[N:5]([CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:7][N:8]=1.Cl.[CH3:19][C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[N:26]=[C:25]([C:30](O)=[O:31])[N:24]=[CH:23]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[C:66]([OH:72])([C:68]([F:71])([F:70])[F:69])=[O:67]>CN1C(=O)CCC1.CS(C)=O.C(#N)C.O>[CH3:19][C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[N:26]=[C:25]([C:30]([NH:17][C@H:14]1[CH2:15][CH2:16][N:12]([C:3]3[C:4]4[N:5]([CH:9]=[CH:10][CH:11]=4)[CH:6]=[CH:7][N:8]=3)[CH2:13]1)=[O:31])[N:24]=[CH:23]2.[C:66]([OH:72])([C:68]([F:71])([F:70])[F:69])=[O:67]

Participants

10

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 455997006-Methylquinazoline-2-carboxylic acid--hydrogen chloride (1/1)HCID 90187471HCID 90187471, compound

Product 2

HCID 6422Trifluoroacetic acidYield 51%HCID 75203706HCID 75203706, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

43 mg (0.156 mmol) of (3S)-1-pyrrolo[1,2-a]pyrazin-1-ylpyrrolidin-3-amine dihydrochloride and 33 mg (0.156 mmol) of 6-methylquinazoline-2-carboxylic acid hydrochloride were dissolved in 0.4 mL of NMP. To this mixture was added 85 mg (0.224 mmol) of HATU and 155 μL (0.892 mmol) of N,N-diisopropylethylamine. The mixture was stirred at rt for 30 minutes, then diluted with 3 mL of DMSO and injected directly onto a reverse-phase semi-preparative HPLC system (5-40% acetonitrile/water, 0.1% TFA). Pure fractions were concentrated in vacuo to give 39 mg of the desired product as a TFA salt (51% yield). 1H NMR (400 MHz, CD3OD) δ 9.49 (s, 1 H), 8.04 (d, J=9.1 Hz, 1 H), 7.93 (d, J=6.9 Hz, 2 H), 7.75 (d, J=1.5 Hz, 1 H), 7.70 (d, J=5.9 Hz, 1 H), 7.55 (s, 1 H), 6.92 (s, 1 H), 6.85 (d, J=5.5 Hz, 1 H), 5.00-3.70 (m, 5 H), 3.30 (s, 3 H), 2.60-2.30 (m, 2 H); MS: (ES) m/z calculated for C21H20N6O [M+H]+ 373.2, found 373.

Workup

  1. concentrationPure fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-2bcc60279bf5468f91e67fd03142da90
Source dataset
uspto-grants-2015_10
Patent number
US09169261B2

Reaction notes

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