Diisopropylethylamine → HCID 71286078, compound

HRID 246212Notes

Reaction equation

HRID 246212 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[F:34][C:35]1[CH:43]=[C:42]2[C:38]([C:39]([C:45]3[N:46]=[C:47]4[C:53]([C:54](O)=[O:55])=[CH:52][N:51]([CH2:57][O:58][CH2:59][CH2:60][Si:61]([CH3:64])([CH3:63])[CH3:62])[C:48]4=[N:49][CH:50]=3)=[N:40][N:41]2[CH3:44])=[CH:37][CH:36]=1.[NH2:65][CH:66]([CH3:75])[CH:67]([CH:69]1[CH2:74][CH2:73][O:72][CH2:71][CH2:70]1)[OH:68].C([O-])(O)=O.[Na+]>CCOC(C)=O.CN(C=O)C>[OH:68][CH:67]([CH:69]1[CH2:70][CH2:71][O:72][CH2:73][CH2:74]1)[CH:66]([NH:65][C:54]([C:53]1[C:47]2[C:48](=[N:49][CH:50]=[C:45]([C:39]3[C:38]4[C:42](=[CH:43][C:35]([F:34])=[CH:36][CH:37]=4)[N:41]([CH3:44])[N:40]=3)[N:46]=2)[N:51]([CH2:57][O:58][CH2:59][CH2:60][Si:61]([CH3:63])([CH3:62])[CH3:64])[CH:52]=1)=[O:55])[CH3:75]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 62386834HCID 62386834, compoundHCID 712796202-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 71286078HCID 71286078, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

In a 100 mL round-bottomed flask, HBTU (112 mg, 0.29 mmol), Hunig's base (0.20 ml, 1.13 mmol) and 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (100 mg, 0.23 mmol) were combined with DMF (3.0 ml) to give a light yellow solution. 2-Amino-1-(tetrahydro-2H-pyran-4-yl)propan-1-ol (72 mg, 0.45 mmol) was added and the reaction mixture was stirred at 25° C. for 16 h. The reaction mixture was diluted with EtOAc. The reaction mixture was poured into 50 mL sat NaHCO3 and extracted with EtOAc (2×50 mL). The organic layers were combined and washed with H2O (2×50 mL) then dried over MgSO4 and concentrated in vacuo to provide the crude material. The product was purified by flash chromatography (silica gel, 80 g, 20% to 50% EtOAc in hexanes) to provide 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [2-hydroxy-1-methyl-2-(tetrahydro-pyran-4-yl)-ethyl]-amide as two discreet diastereomers (arbitrarily assigned). Diastereomer A (30 mg, 22%) as a white powder: 1H NMR (300 MHz, CDCl3) δ ppm 9.20 (m, 1H), 8.68 (dd, J=8.69, 5.29 Hz, 1H), 8.41 (d, J=9.44 Hz, 1H), 8.27 (s, 1H) 6.96-7.13 (m, 2H) 5.70 (s, 2H) 4.54-4.67 (m, 1H) 4.06-4.20 (m, 4H) 3.87-4.04 (m, 2H) 3.56-3.65 (m, 2H) 3.42 (d, J=6.80 Hz, 1H) 3.21-3.39 (m, 2H), 2.53 (d, J=4.15 Hz, 1H) 1.85 (d, J=12.84 Hz, 2H) 1.76 (ddd, J=11.52, 7.93, 3.97 Hz, 1H), 1.33-1.56 (m, 5H), 0.75-1.04 (m, 2H), −0.05 (s, 9H). Diastereomer B (70 mg, 53%) as a white powder: 1H NMR (300 MHz, CDCl3) δ ppm 9.21 (s, 1H) 8.42-8.61 (m, 2H) 8.27 (s, 1H) 6.96-7.15 (m, 2H) 5.51-5.76 (m, 2H) 4.40-4.64 (m, 1H) 3.93-4.24 (m, 3H) 3.62-3.83 (m, 2H) 3.50-3.62 (m, 2H) 3.26-3.50 (m, 2H) 2.70 (d, J=5.29 Hz, 1H) 1.92-2.10 (m, 2H) 1.14-1.84 (m, 5H) 0.67-1.07 (m, 2H) −0.33-0.16 (m, 9H).

Workup

  1. customto give a light yellow solution
  2. additionThe reaction mixture was poured into 50 mL
  3. extractionextracted with EtOAc (2×50 mL)
  4. washwashed with H2O (2×50 mL)
  5. dry with materialthen dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customto provide the crude material
  8. customThe product was purified by flash chromatography (silica gel, 80 g, 20% to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-eb98170f22f4447ba7f57703e2d7efa6
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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