Dichloromethane → HCID 72695031, compound

HRID 874742Notes

Reaction equation

HRID 874742 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([NH:11][C:12](=[O:24])[CH:13]([N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)[C:14]3[CH:18]=[CH:17][S:16][CH:15]=3)[CH:9]=2)[NH:4][N:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH:38]=[CH:37][C:36]([N:39]3[CH2:45][C:41]4([CH2:44][O:43][CH2:42]4)[CH2:40]3)=[CH:35][CH:34]=2)O1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.CCOC(C)=O>[CH2:44]1[C:41]2([CH2:45][N:39]([C:36]3[CH:37]=[CH:38][C:33]([C:2]4[C:10]5[C:5](=[CH:6][CH:7]=[C:8]([NH:11][C:12](=[O:24])[CH:13]([N:19]6[CH2:23][CH2:22][CH2:21][CH2:20]6)[C:14]6[CH:18]=[CH:17][S:16][CH:15]=6)[CH:9]=5)[NH:4][N:3]=4)=[CH:34][CH:35]=3)[CH2:40]2)[CH2:42][O:43]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 86706886HCID 86706886, compoundHCID 178521833HCID 178521833, compound

Product 1

HCID 72695031HCID 72695031, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
130 °C

Procedure

The title compound was synthesized according to General Method C1 by utilizing N-(3-iodo-1H-indazol-5-yl)-2-(pyrrolidin-1-yl)-2-(thiophen-3-yl)acetamide (200 mg, 0.45 mmol), 6-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-oxa-6-azaspiro[3.3]heptane (160 mg, 0.53 mmol), PdCl2dppf.DCM (36 mg, 0.044 mmol) and 2 M aq Na2CO3 (0.5 mL) in PhMe/EtOH (12 mL, 2:1 mixture). The reaction mixture was heated under microwave irradiation at 130° C. for 3 h. The reaction mixture was diluted with EtOAc (10 mL) and washed with H2O (5 mL), dried (MgSO4) and concentrated under vacuum to give a crude product. Purification by flash chromatography (Biotage Isolera, 50 g HP-SIL, 100% EtOAc then 0-10% DCM in MeOH) followed by trituration with MeOH gave the title compound as a light brown solid (46 mg, 18%). 1H NMR (400 MHz, CDCl3) δ ppm 9.21 (br. s., 1H), 8.38 (s, 1H), 7.83 (d, J=8.0 Hz, 2H), 7.48 (d, J=9.0 Hz, 1H), 7.42 (d, J=8.8 Hz, 1H), 7.29-7.36 (m, 2H), 7.15 (d, J=4.8 Hz, 1H), 6.58 (d, J=8.3 Hz, 2H), 4.87 (s, 4H), 4.15 (s, 1H), 4.09 (s, 4H), 2.61-2.75 (m, 2H), 2.47-2.60 (m, 2H), 1.76-1.92 (m, 4H); MS ESI 500.3 [M+H]+, calcd for [C28H29N5O2S+H]+ 500.2.

Workup

  1. washwashed with H2O (5 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated under vacuum
  4. customto give a crude product

Sources & evidence

ORD record
ord-8d3624414c8a47059c87cb29df3503a3
Source dataset
uspto-grants-2015_03
Patent number
US08980934B2

Reaction notes

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