Acetonitrile → Ammonium Hydroxide

HRID 630722Notes

Reaction equation

HRID 630722 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([NH:17][C:18]([NH:20][C@@H:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C@H:24]([O:31][C:32]3[CH:33]=[CH:34][C:35]4[N:36]([C:38]([CH2:41][CH:42]5[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]5)=[N:39][N:40]=4)[CH:37]=3)[CH2:23][CH2:22]2)=[O:19])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.FC(F)(F)S(O[CH2:63][CH:64]([F:66])[F:65])(=O)=O.CC#N>C(Cl)Cl.CO.O>[NH4+:8].[OH-:19].[C:1]([C:5]1[CH:6]=[C:7]([NH:17][C:18]([NH:20][C@@H:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C@H:24]([O:31][C:32]3[CH:33]=[CH:34][C:35]4[N:36]([C:38]([CH2:41][CH:42]5[CH2:43][CH2:44][N:45]([CH2:63][CH:64]([F:66])[F:65])[CH2:46][CH2:47]5)=[N:39][N:40]=4)[CH:37]=3)[CH2:23][CH2:22]2)=[O:19])[N:8]([C:10]2[CH:11]=[CH:12][C:13]([CH3:16])=[CH:14][CH:15]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 81531Diisopropylethylamine2×HCID 27740892,2-Difluoroethyl trifluoromethanesulfonate2×HCID 866869851-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1S,4R)-4-(3-piperidin-4-ylmethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea

Product 2

HCID 14923Ammonium HydroxideYield 0.1%HCID 86686987HCID 86686987, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 21226129Dichloromethane methanolSolvent

Procedure

To an orange solution of Intermediate 22d (58 mg, 0.0917 mmol) and DIPEA (0.0319 mL, 0.183 mmol) in DCM-MeOH (4:1, 2.5 mL), was added 2,2-difluoroethyl trifluoromethane-sulfonate (Fluorochem, 29.4 mg, 0.138 mmol) and the solution stirred at RT for 2 h. DIPEA (0.0319 mL, 0.183 mmol) and 2,2-difluoroethyl trifluoromethanesulfonate (29.4 mg, 0.138 mmol) were added sequentially, and the pale green solution stirred at RT for 1 h. Water (2 mL) was added and the mixture extracted with DCM (2×3 mL). The combined organics were passed through a hydrophobic frit and concentrated in vacuo to leave a pale green-brown solid. HPLC (XBridge C18, 50-98% MeCN in H2O, 0.1% NH4OH) gave the title compound as a white solid after freeze-drying (11.5 mg, 18%). LCMS (Method 5): Rt 3.75 min, m/z 697 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.22 (9H, s), 1.24-1.33 (2H, m), 1.59 (2H, d, J 13.0), 1.75-1.92 (3H, m), 2.01-2.10 (4H, m), 2.31 (3H, s), 2.62 (2H, td, J 15.8, 4.8), 2.82 (2H, d, J 11.4), 2.98 (2H, d, J 7.2), 4.78 (1H, m), 5.48 (1H, t, J 4.7), 6.04 (1H, tt, J 55.7, 4.4), 6.27 (1H, s), 7.07 (1H, d, J 8.9), 7.11 (1H, dd, J 10.0, 2.2), 7.21-7.35 (8H, m), 7.63 (1H, d, J 9.8), 8.03 (1H, s), 8.17 (1H, d, J 2.0).

Workup

  1. stirringthe pale green solution stirred at RT for 1 h
  2. extractionthe mixture extracted with DCM (2×3 mL)
  3. concentrationconcentrated in vacuo
  4. customto leave a pale green-brown solid

Sources & evidence

ORD record
ord-ce06c8eeba4c452b97a4812855f5922b
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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