Ethanolamine → HCID 70818836, compound

HRID 331504Notes

Reaction equation

HRID 331504 reaction equation
F[B-](F)(F)F.N1(OC(=[N+](C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:23][C:24]1[N:25]=[CH:26][C:27]([C:41]2[CH:46]=[CH:45][N:44]=[C:43]([C:47]([CH3:52])([CH3:51])[C:48]([OH:50])=O)[CH:42]=2)=[N:28][C:29]=1[C:30]1[O:34][N:33]=[C:32]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:31]=1.C(N(C(C)C)CC)(C)C.[NH2:62][CH2:63][CH2:64][OH:65]>ClCCl.C(OCC)(=O)C.[Cl-].[Na+].O>[NH2:23][C:24]1[N:25]=[CH:26][C:27]([C:41]2[CH:46]=[CH:45][N:44]=[C:43]([C:47]([CH3:52])([CH3:51])[C:48]([NH:62][CH2:63][CH2:64][OH:65])=[O:50])[CH:42]=2)=[N:28][C:29]=1[C:30]1[O:34][N:33]=[C:32]([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:31]=1

Participants

7

Reactant 4

HCID 700EthanolamineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 70818609HCID 70818609, compound

Product 1

HCID 70818836HCID 70818836, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 131718255Brine ethyl acetateSolvent

Procedure

(benzotriazol-1-yloxy-dimethylamino-methylene)-dimethyl-ammonium tetrafluoroborate (10.40 mg, 0.03239 mmol) was added to a stirred solution of 2-[4-[5-amino-6-(3-phenylisoxazol-5-yl)pyrazin-2-yl]-2-pyridyl]-2-methyl-propanoic acid (13 mg, 0.03239 mmol), diisopropyl ethyl amine (5.442 mg, 7.334 μL, 0.04211 mmol) and 2-aminoethanol (9.895 mg, 9.778 μL, 0.1620 mmol) in dichloromethane (15 mL) and the reaction allowed to stir at ambient temperature for 1 hour. The reaction was diluted with ethyl acetate/brine. The aqueous layer was extracted with ethyl acetate (×1) and the combined organic extracts washed with brine (×1). The organic extracts were then dried over MgSO4, filtered and concentrated in vacuo. Compound was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% trifluoroacetic acid in water; solvent B: acetonitrile) over 16 minutes at 25 mL/minutes], combined fractions were then freeze-dried to give 2-[4-[5-amino-6-(3-phenylisoxazol-5-yl)pyrazin-2-yl]-2-pyridyl]-N-(2-hydroxyethyl)-2-methyl-pro panamide Compound I-46 as a yellow solid (4 mg, 21.67%). 1H NMR (400.0 MHz, MeOD) δ 1.8 (s, 6H), 3.4 (t, 2H), 3.7 (t, 2H), 7.53-7.57 (m, 3H), 7.62 (s, 1H), 8.0-8.05 (m, 2H), 8.42 (d, 1H), 8.48 (s, 1H), 8.7 (d, 1H), 9.03 (s, 1H); LC/MS m/z 445.1 [M+H]+.

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate (×1)
  2. washthe combined organic extracts washed with brine (×1)
  3. dry with materialThe organic extracts were then dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customCompound was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% trifluoroacetic acid in water; solvent B: acetonitrile) over 16 minutes at 25 mL/minutes]
  7. customwere then freeze-dried

Sources & evidence

ORD record
ord-7b6507d65c02494da64ef4c22b27b53e
Source dataset
uspto-grants-2014_11
Patent number
US08877759B2

Reaction notes

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