Diisopropylethylamine → Trifluoroacetic acid

HRID 1184586Notes

Reaction equation

HRID 1184586 reaction equation
[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:19][N:14]4[CH2:15][CH2:16][NH:17][CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[F:20][C:21]([F:32])([F:31])[C:22]1[CH:27]=[CH:26][N:25]=[C:24]([C:28](O)=[O:29])[CH:23]=1.Cl.C(N=C=NCCCN(C)C)C.[OH2:45].[OH:46]N1C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>ClCCl>[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:19][N:14]4[CH2:15][CH2:16][N:17]([C:28]([C:24]5[CH:23]=[C:22]([C:21]([F:32])([F:20])[F:31])[CH:27]=[CH:26][N:25]=5)=[O:29])[CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[F:20][C:21]([F:32])([F:31])[C:22]([OH:46])=[O:45]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 120251644-(Trifluoromethyl)pyridine-2-carboxylic acidHCID 86680449(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]octahydropyrrolo[1,2-a]pyrazine

Product 2

HCID 6422Trifluoroacetic acidHCID 86680507[(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]hexahydropyrrolo[1,2-a]-pyrazin-2(1H)-yl][4-(trifluoromethyl)pyridin-2-yl]methanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of the product from Example 54F (30 mg, 0.115 mmol) and 4-(trifluoromethyl)picolinic acid (26.4 mg, 0.138 mmol) in dichloromethane (1 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (33.1 mg, 0.173 mmol) followed by 1-hydroxybenzotriazole hydrate (26.5 mg, 0.173 mmol) and Hunig's base (0.040 mL, 0.230 mmol). The resulting solution was stirred at ambient temperature for 90 minutes. The mixture was partitioned between water (1 mL) and dichloromethane (3×1 mL), and the combined dichloromethane layers were concentrated in vacuo. The crude product was purified by column chromatography on C-18 reverse-phase silica gel using a solvent gradient of 0-100% acetonitrile in water (0.1% trifluoroacetic acid). The fractions containing pure product were pooled and concentrated in vacuo to give the title compound as a trifluoroacetic acid salt. 1H NMR (300 MHz, CDCl3) δ ppm 5.55-5.65 (m, 1 H), 7.65 (d, J=5.16 Hz, 1 H), 7.90-8.00 (m, 1 H), 8.03-8.13 (m, 2 H), 8.77 (t, J=5.35 Hz, 1 H); MS (ESI) m/z 434.1 (M+H)+.

Workup

  1. customThe mixture was partitioned between water (1 mL) and dichloromethane (3×1 mL)
  2. concentrationthe combined dichloromethane layers were concentrated in vacuo
  3. customThe crude product was purified by column chromatography on C-18 reverse-phase silica gel using a solvent gradient of 0-100% acetonitrile in water (0.1% trifluoroacetic acid)
  4. additionThe fractions containing pure product
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2e14c22c80ee4b3f9cbb64f46ecb6c09
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

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