Diisopropylethylamine → HCID 57405175, compound

HRID 1520090Notes

Reaction equation

HRID 1520090 reaction equation
CS(OS(C)(=O)=O)(=O)=O.[N:10]1([C:16]([C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH:28]=[C:27]([C:29]4[C:37]5[C:32](=[CH:33][CH:34]=[C:35]([CH2:38][OH:39])[CH:36]=5)[N:31](C5CCCCO5)[N:30]=4)[N:26]=[N:25]3)=[CH:20][CH:19]=2)=[O:17])[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.CCN(C(C)C)C(C)C.O[C@@H:56]1[CH2:61][O:60][C:58](=[O:59])[CH2:57]1>C(Cl)Cl>[N:10]1([C:16]([C:18]2[CH:19]=[CH:20][C:21]([N:24]3[CH:28]=[C:27]([C:29]4[C:37]5[C:32](=[CH:33][CH:34]=[C:35]([CH2:38][O:39][C@@H:56]6[CH2:61][O:60][C:58](=[O:59])[CH2:57]6)[CH:36]=5)[NH:31][N:30]=4)[N:26]=[N:25]3)=[CH:22][CH:23]=2)=[O:17])[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 81560Methanesulfonic anhydrideHCID 72693893-Hydroxybutyrolactone, (3S)-HCID 68061561HCID 68061561, compound

Product 1

HCID 57405175HCID 57405175, compoundYield 7.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of methanesulfonic anhydride (113 mg; 0.65 mmol; 1.6 eq.) in DCM (3.0 mL) was added dropwise over 1 min to a solution of [3-{1-[4-(morpholin-4-ylcarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl]methanol (194 mg; 0.40 mmol; 1.0 eq.) in DIEA (1.0 mL; 5.9 mmol; 15 eq.) and DCM (3.0 mL) containing activated molecular sieves. After 10 min, a solution of (S)-3-hydroxy-g-butyrolactone (160 mg; 1.57 mmol; 4 eq.) in DCM (1.0 mL) was added dropwise over 2 min. The reaction mixture was then stirred for 16 h at RT. It was filtered through a celite pad and the filtrate was concentrated under reduced pressure. The residue was redissolved in MeOH (2 mL) and hydrogen chloride (8 mL of a 4N solution in dioxane) was added. The reaction mixture was stirred at RT for 3 h and then concentrated under reduced pressure. Purification by preparative HPLC gave the title compound as a white solid (14 mg, 7%). 1H NMR (300 MHz, DMSO-d6) δ 13.41 (s, 1H), 9.38 (s, 1H), 8.33 (s, 1H), 8.15 (d, J=8.5 Hz, 2H), 7.69 (d, J=8.5 Hz, 2H), 7.61 (d, J=8.6 Hz, 1H), 7.49-7.37 (m, 1H), 4.69 (s, 2H), 4.47-4.34 (m, 3H), 3.82-3.40 (m, 8H), 2.88 (dd, J=17.8, 5.7 Hz, 1H), 2.56 (d, J=17.8 Hz, 1H). HPLC (max plot) 96.5%; Rt %2.59 min. UPLC/MS: (MS+) 489.5, (MS−) 487.6.

Workup

  1. additioncontaining
  2. filtrationIt was filtered through a celite pad
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. dissolutionThe residue was redissolved in MeOH (2 mL)
  5. additionhydrogen chloride (8 mL of a 4N solution in dioxane) was added
  6. stirringThe reaction mixture was stirred at RT for 3 h
  7. concentrationconcentrated under reduced pressure
  8. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-767ad33b2fcb4c7ca54683a22dfcdb54
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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