2,3-Dihydrofuran → HCID 68162420, compound

HRID 521602Notes

Reaction equation

HRID 521602 reaction equation
[CH3:1][CH:2]([NH:4][CH2:5][CH2:6][CH2:7][N:8]1[C:17]([S:18][C:19]2[CH:24]=[C:23]3[O:25][CH2:26][O:27][C:22]3=[CH:21][C:20]=2I)=[N:16][C:10]2[C:11]([NH2:15])=[N:12][CH:13]=[N:14][C:9]1=2)[CH3:3].CCN(C(C)C)C(C)C.[O:38]1[CH:42]=[CH:41][CH2:40][CH2:39]1>CN1C(=O)CCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:23][OH:25].[NH3:4].[O:38]1[CH:39]=[CH:40][CH2:41][CH:42]1[C:20]1[C:19]([S:18][C:17]2[N:8]([CH2:7][CH2:6][CH2:5][NH:4][CH:2]([CH3:3])[CH3:1])[C:9]3[C:10]([N:16]=2)=[C:11]([NH2:15])[N:12]=[CH:13][N:14]=3)=[CH:24][C:23]2[O:25][CH2:26][O:27][C:22]=2[CH:21]=1

Participants

7

Reactant 3

HCID 709342,3-DihydrofuranHCID 81531DiisopropylethylamineHCID 9549213Zelavespib

Product 2

HCID 21705897Ammonia methanolHCID 68162420HCID 68162420, compoundYield 52.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
55 °C

Procedure

A solution of PU-H71 (30 mg, 0.0585 mmol) in NMP (1.5 mL) was evacuated and back filled with nitrogen. This was repeated four times, then DIEA (15.1 mg, 21 μL, 0.117 mmol), 2,3-dihydrofuran (82 mg, 88 μL, 1.17 mmol) and Pd(PPh3)4 (13.5 mg, 0.0117 mmol) were added and the reaction mixture was heated under nitrogen at 55° C. for 20 h. Solvent was removed under reduced pressure and the resulting residue was purified by preparatory TLC two times (hexane:EtOAc:CH2Cl2:MeOH—NH3 (7N), 2:1:2:0.5, then CH2Cl2:MeOH—NH3 (7N), 15:1) to give 7.0 mg (26%) of DZ3-142. 1H NMR (500 MHz, CDCl3) δ 8.23 (s, 1H), 7.06 (s, 1H), 6.96 (s, 1H), 6.43 (m, 1H), 6.01 (s, 2H), 5.94 (dd, J=8.1, 10.8 Hz, 1H), 5.72 (br s, 2H), 4.93 (m, 1H), 4.35 (t, J=6.8 Hz, 2H), 2.95-3.55 (m, 2H), 2.70 (t, J=6.5 Hz, 2H), 2.39-2.47 (m, 1H), 2.22 (m, 2H), 1.25 (d, J=6.2 Hz, 6H); HRMS (ESI) m/z [M+H]+ calcd. for C22H27H6O3S, 455.1865; found. 455.1865; HPLC: method A Rt=6.07, method B Rt=6.49.

Workup

  1. additionback filled with nitrogen
  2. customSolvent was removed under reduced pressure
  3. customthe resulting residue was purified by preparatory TLC two times (hexane

Sources & evidence

ORD record
ord-7554d7872e004f788957e187ac6b6c82
Source dataset
uspto-grants-2016_05
Patent number
US09328114B2

Reaction notes

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