Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → HCID 59344942, compound

HRID 19156Notes

Reaction equation

HRID 19156 reaction equation
[Li+].[CH3:2][N:3]([CH3:26])[C:4]1[C:5]([F:25])=[C:6]([CH:22]=[CH:23][CH:24]=1)[O:7][C:8]1[CH2:12][N:11]([C@@H:13]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:14]([O-])=[O:15])[C:10](=[O:21])[CH:9]=1.[CH3:27][C:28]1([CH3:40])[O:32][C@H:31]([CH2:33][N:34]2[CH:38]=[CH:37][C:36]([NH2:39])=[N:35]2)[CH2:30][O:29]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[CH3:27][C:28]1([CH3:40])[O:32][C@H:31]([CH2:33][N:34]2[CH:38]=[CH:37][C:36]([NH:39][C:14](=[O:15])[C@@H:13]([N:11]3[CH2:12][C:8]([O:7][C:6]4[CH:22]=[CH:23][CH:24]=[C:4]([N:3]([CH3:2])[CH3:26])[C:5]=4[F:25])=[CH:9][C:10]3=[O:21])[CH2:17][CH:18]([CH3:20])[CH3:19])=[N:35]2)[CH2:30][O:29]1

Participants

5

Reactant 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 59344941(R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amineHCID 67504629(s)-2-[4-(3-Dimethylamino-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid lithium salt

Product 1

HCID 59344942HCID 59344942, compoundYield 51.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-2-[4-(3-dimethylamino-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid lithium salt (0.257 g, 0.73 mmol) in N,N-dimethylformamide (5 mL) was added 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-ylamine (prepared as in Example 49, 0.160 g, 0.81 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (1.91 g, 4.32 mmol). The mixture was stirred at room temperature overnight and the solvents were evaporated. The residue was treated with ethyl acetate and ammonium chloride solution, and the organic layer separated. The organic layer was washed with a saturated sodium chloride solution and dried over sodium sulfate. The solvents were evaporated and the residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 25 g, 10% to 75% ethyl acetate/hexanes) which afforded (S)-2-[4-(3-dimethylamino-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (0.200 g, 51%) as a yellow solid: HR-ES-MS m/z calculated for C27H36FN5O5 [M+H]+ 530.2773, observed 530.2771, 1H NMR (300 MHz, DMSO-d6) δ ppm 1.00 0.90 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H), 1.25 (s, 3H), 1.31 (d, J=3.0 Hz, 3H), 1.38-1.50 (m, 1H), 1.50-1.65 (m, 1H), 1.69-1.85 (m, 1H), 2.82 (s, 6H), 3.74 (dd, J=8.3, 5.9 Hz, 1H), 4.01 (dd, J=8.5, 6.3 Hz, 1H), 4.04-4.15 (m, 2H), 4.20 (d, J=18.4 Hz, 1H), 4.29-4.43 (m, 1H), 4.58 (d, J=18.4 Hz, 1H), 4.86 (s, 1H), 4.87-4.95 (m, 1H), 6.44 (d, J=2.1 Hz, 1H), 6.79-6.98 (m, 2H), 7.12 (t, J=8.5 Hz, 1H), 7.61 (br. s., 1H), 10.80 (s, 1H).

Workup

  1. customthe solvents were evaporated
  2. additionThe residue was treated with ethyl acetate and ammonium chloride solution
  3. customthe organic layer separated
  4. washThe organic layer was washed with a saturated sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. customThe solvents were evaporated
  7. customthe residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 25 g, 10% to 75% ethyl acetate/hexanes) which

Sources & evidence

ORD record
ord-03edb212b591483080725095a1f7a2f7
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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