Triethylamine → HCID 52938543, compound

HRID 1053739Notes

Reaction equation

HRID 1053739 reaction equation
C1N=CN([C:6](N2C=NC=C2)=[O:7])C=1.Cl.[NH2:14][C@@H:15]1[CH2:24][CH2:23][CH2:22][C:21]2[C:20]([C:25]3[N:29]=[C:28]([C:30]4[CH:31]=[CH:32][C:33]([O:38][CH:39]([CH3:41])[CH3:40])=[C:34]([CH:37]=4)[C:35]#[N:36])[O:27][N:26]=3)=[CH:19][CH:18]=[CH:17][C:16]1=2.CCN(CC)CC.[CH3:49][N:50]([CH3:56])[C@@H:51]1[CH2:55][CH2:54][NH:53][CH2:52]1>C(Cl)Cl>[C:35]([C:34]1[CH:37]=[C:30]([C:28]2[O:27][N:26]=[C:25]([C:20]3[CH:19]=[CH:18][CH:17]=[C:16]4[C:21]=3[CH2:22][CH2:23][CH2:24][C@H:15]4[NH:14][C:6]([N:53]3[CH2:54][CH2:55][C@@H:51]([N:50]([CH3:56])[CH3:49])[CH2:52]3)=[O:7])[N:29]=2)[CH:31]=[CH:32][C:33]=1[O:38][CH:39]([CH3:41])[CH3:40])#[N:36]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 2758521(3R)-(+)-3-(Dimethylamino)pyrrolidineHCID 67198744HCID 67198744, compound

Product 1

HCID 52938543HCID 52938543, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Prepared using General Procedure 3: To a stirring solution of CDI ((9.5 mg, 0.06 mmol) in DCM (1 mL) were added dropwise a solution of (R)-5-(3-(5-amino-5,6,7,8-tetrahydronaphthalen-1-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile HCl salt 3 (20 mg, 0.05 mmol) and Et3N (20.3 μL, 0.15 mmol) in DCM (1 mL). After stirring for 15 h at room temperature, this solution was added dropwise to another solution containing (R)-3-dimethylaminopyrrolidine (18.6 mg, 0.15 mmol)) in DCM (1 mL) at room temperature. The reaction was stirred at room temperature for 6.5 h. The solvent was evaporated and the pure product was isolated by preparative HPLC to afford 17.5 mg (70%) of (R)-N-((R)-5-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)-3-(dimethylamino) pyrrolidine-1-carboxamide 20. LCMS-ESI (m/z) calculated for C29H34N6O3: 514.6; found 515.3 [M+H]+, tR=2.56 min. 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J=2.2 Hz, 1H), 8.31 (dt, J=8.7, 4.3 Hz, 1H), 7.91 (d, J=7.6 Hz, 1H), 7.52 (d, J=7.6 Hz, 1H), 7.34 (t, J=7.7 Hz, 1H), 7.12 (d, J=9.2 Hz, 1H), 5.13 (d, J=6.9 Hz, 1H), 4.86-4.73 (m, 1H), 4.64 (d, J=8.2 Hz, 1H), 3.91 (dd, J=10.4, 7.3 Hz, 1H), 3.80-3.56 (m, 3H), 3.41 (dd, J=17.5, 8.3 Hz, 1H), 3.15 (d, J=18.0 Hz, 1H), 3.10-2.93 (m, 1H), 2.85 (s, 6H), 2.46 (m, 2H), 2.05 (dd, J=9.2, 4.8 Hz, 1H), 1.88 (m, 3H), 1.45 (dd, J=13.9, 6.1 Hz, 6H).

Workup

  1. customPrepared
  2. additionthis solution was added dropwise to another solution
  3. stirringThe reaction was stirred at room temperature for 6.5 h
  4. customThe solvent was evaporated
  5. customthe pure product was isolated by preparative HPLC

Sources & evidence

ORD record
ord-a77e5774773540bcb40941bba8eedaa6
Source dataset
uspto-grants-2016_07
Patent number
US09394264B2

Reaction notes

Loading…