Trifluoroacetic acid → HCID 75203705, compound

HRID 1755221Notes

Reaction equation

HRID 1755221 reaction equation
[ClH:1].Cl.[CH3:3][C:4]1[CH:5]=[CH:6][N:7]2[CH:12]=[CH:11][N:10]=[C:9]([N:13]3[CH2:17][CH2:16][C@H:15]([NH2:18])[CH2:14]3)[C:8]=12.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]2[CH:30]=[CH:29][C:28]([C:31](O)=[O:32])=[N:27]2)=[CH:22][CH:21]=1.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(O)(C(F)(F)F)=O>CN1C(=O)CCC1.CS(C)=O.C(#N)C.O>[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([N:26]2[CH:30]=[CH:29][C:28]([C:31]([NH:18][C@H:15]3[CH2:16][CH2:17][N:13]([C:9]4[C:8]5[N:7]([CH:6]=[CH:5][C:4]=5[CH3:3])[CH:12]=[CH:11][N:10]=4)[CH2:14]3)=[O:32])=[N:27]2)=[CH:24][CH:25]=1.[ClH:1]

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 141293761-(4-chlorophenyl)-1H-pyrazole-3-carboxylic acidHCID 86720521HCID 86720521, compound

Product 2

HCID 313Hydrochloric AcidYield 78%HCID 75203705HCID 75203705, compoundYield 84.4%

Reagents, catalysts & solvents 3

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

Procedure

40 mg (0.138 mmol) of (3S)-1-(8-methylpyrrolo[1,2-a]pyrazin-1-yl)pyrrolidin-3-amine dihydrochloride and 31 mg (0.138 mmol) of 1-(4-chlorophenyl)pyrazole-3-carboxylic acid were dissolved in 0.5 mL of NMP. To this mixture were added 79 mg (0.207 mmol) of HATU and 0.120 mL (0.690 mmol) of N,N-diisopropylethylamine. The mixture was stirred at rt for 1 hour, then diluted with 3 mL of DMSO and injected directly onto a reverse-phase semi-preparative HPLC system (5-60% acetonitrile/water, 0.1% TFA). Pure fractions were concentrated in vacuo, dissolved in 1 mL of methanol and passed through a bicarbonate resin cartridge (PL-HCO3 MP SPE 500 mg/6 mL). To the resulting solution 15 μL of concentrated hydrochloric acid was added and the volatiles were removed in vacuo to give 49 mg of the desired product as an HCl salt (78% yield). 1H NMR (400 MHz, DMSO) δ 11.38 (s, 1 H), 8.78 (d, J=7.0 Hz, 1 H), 8.59 (d, J=3.0 Hz, 1 H), 7.95 (d, J=7.0, 2 H), 7.81 (m, 2 H), 7.61 (d, J=8.8 Hz, 2 H), 6.92 (s, 1 H), 6.85 (d, J=5.5 Hz, 1 H), 6.76 (d, J=2.2 Hz, 1 H), 4.70-4.65 (m, 1 H), 4.18-3.80 (m, 4 H), 2.48 (s, 3 H), 2.38-2.18 (m, 2 H); MS: (ES) m/z calculated for C22H21ClN6O [M+H]+ 421.2, found 421.

Workup

  1. concentrationPure fractions were concentrated in vacuo
  2. dissolutiondissolved in 1 mL of methanol
  3. additionTo the resulting solution 15 μL of concentrated hydrochloric acid was added
  4. customthe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-f34c6b0347234963b7e37fc9b4bae227
Source dataset
uspto-grants-2015_10
Patent number
US09169261B2

Reaction notes

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