Diisopropylethylamine → 1-[(1S,4S)-4-(3-Isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3-(1-p-tolyl-1H-pyrazol-4-yl)-urea

HRID 75580Notes

Reaction equation

HRID 75580 reaction equation
ClC(Cl)(Cl)CO[C:5](=[O:19])[NH:6][C:7]1[CH:8]=[N:9][N:10]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)[CH:11]=1.[CH:22]([C:25]1[N:29]2[CH:30]=[C:31]([O:34][C@@H:35]3[C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[C@@H:38]([NH2:45])[CH2:37][CH2:36]3)[CH:32]=[CH:33][C:28]2=[N:27][N:26]=1)([CH3:24])[CH3:23].CCN(C(C)C)C(C)C>CN(C=O)C>[CH:22]([C:25]1[N:29]2[CH:30]=[C:31]([O:34][C@@H:35]3[C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[C@@H:38]([NH:45][C:5]([NH:6][C:7]4[CH:8]=[N:9][N:10]([C:12]5[CH:13]=[CH:14][C:15]([CH3:18])=[CH:16][CH:17]=5)[CH:11]=4)=[O:19])[CH2:37][CH2:36]3)[CH:32]=[CH:33][C:28]2=[N:27][N:26]=1)([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 86686683(1S,4S)-4-(3-Isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-ylamineHCID 86686685(1-p-Tolyl-1H-pyrazol-4-yl)-carbamic acid 2,2,2-trichloro-ethyl ester

Product 1

HCID 866866861-[(1S,4S)-4-(3-Isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3-(1-p-tolyl-1H-pyrazol-4-yl)-ureaYield 77.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of Intermediate 6c (65.0 mg, 0.19 mmol), Intermediate 5c (50.0 mg, 0.155 mmol), and DIPEA (0.127 mL, 0.8 mmol) in DMF (1 mL) was heated at 110° C. for 75 min and 50° C. for 64 h. After cooling, the mixture was concentrated to dryness and the residue purified by FCC, eluting with 0-10% MeOH in DCM, to give the impure product (63 mg). Further purification by HPLC (Method 6) gave the title compound as a white solid (45 mg, 56%). LCMS (Method 5): Rt 4.06 min, m/z 522.1 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.36-1.41 (6H, m), 1.76-1.85 (1H, m), 1.98-2.08 (1H, m), 2.13-2.28 (2H, m), 2.33 (3H, s), 3.59 (1H, quintet, J 6.8), 4.96-5.03 (1H, m), 5.62 (1H, t, J 4.6), 6.74 (1H, d, J 8.5), 7.24 (1H, dd, J 9.9, 2.1), 7.26-7.46 (6H, m), 7.62-7.66 (2H, m), 7.68 (1H, s), 7.70 (1H, dd, J 9.9, 0.8), 8.24 (1H, br d), 8.26 (1H, s), 8.31 (1H, s).

Workup

  1. temperatureAfter cooling
  2. concentrationthe mixture was concentrated to dryness
  3. customthe residue purified by FCC
  4. washeluting with 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-8f9322f895f04b27aabb531ec9df9549
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

Loading…