Diisopropylethylamine → 1-{4-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]benzoyl}pyrrolidin-3-ol

HRID 1520057Notes

Reaction equation

HRID 1520057 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25]([C:32]2[N:33]=[N:34][N:35]([C:37]3[CH:45]=[CH:44][C:40]([C:41]([OH:43])=O)=[CH:39][CH:38]=3)[CH:36]=2)=[N:24]1.CCN(C(C)C)C(C)C.[NH:55]1[CH2:59][CH2:58][CH:57]([OH:60])[CH2:56]1>CN(C=O)C.C(Cl)Cl>[NH:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25]([C:32]2[N:33]=[N:34][N:35]([C:37]3[CH:45]=[CH:44][C:40]([C:41]([N:55]4[CH2:59][CH2:58][CH:57]([OH:60])[CH2:56]4)=[O:43])=[CH:39][CH:38]=3)[CH:36]=2)=[N:24]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 982104-HydroxypyrrolidineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 679811434-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]benzoic acid

Product 1

HCID 679818451-{4-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]benzoyl}pyrrolidin-3-ol

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of TBTU (137 mg; 0.33 mmol; 1.3 eq.) and 4-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]benzoic acid (100 mg; 0.33 mmol; 1.0 eq.) in DMF (2 mL) was stirred for 1 h at RT before the addition of DIEA (111 μl; 0.66 mmol; 2.0 eq.) and 3-pyrrolidinol (43 mg; 0.49 mmol.; 1.5 eq.). The reaction mixture was stirred at RT overnight. It was then diluted with DCM and washed with an aqueous saturated solution of NaHCO3. Organic phase was dried over magnesium sulfate, filtered and concentrated. The crude was purified by preparative HPLC to afford the title compound as a yellow solid. 1H NMR (300 Mz, DMSO-d6) δ 13.38 (s, 1H), 9.41 (s, 1H), 8.37 (d, J=8.1 Hz, 1H), 8.15 (d, J=8.7 Hz, 2H), 7.78 (dd, J=3.2, 8.6 Hz, 2H), 7.62 (d, J=8.4 Hz, 1H), 7.51-7.39 (m, 1H), 7.27 (t, J=7.1 Hz, 1H), 4.32 (brd, J=26.0 Hz, 1H), 3.76-3.54 (m, 2H), 3.54-3.20 (m, 3H), 2.06-1.75 (m, 2H). HPLC (Condition A): Rt 2.58 min (purity 96.7%). MS (ESI+): 375.2, MS (ESI−): 373.2.

Workup

  1. washwashed with an aqueous saturated solution of NaHCO3
  2. dry with materialOrganic phase was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude was purified by preparative HPLC

Sources & evidence

ORD record
ord-3b6bf45efd1c4ae79b98c30569ab2b01
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

Loading…