2,5-Dihydrofuran → HCID 67115852, compound

HRID 521603Notes

Reaction equation

HRID 521603 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[CH2:42][CH:41]=[CH: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][CH:41]([C:20]2[C:19]([S:18][C:17]3[N:8]([CH2:7][CH2:6][CH2:5][NH:4][CH:2]([CH3:3])[CH3:1])[C:9]4[C:10]([N:16]=3)=[C:11]([NH2:15])[N:12]=[CH:13][N:14]=4)=[CH:24][C:23]3[O:25][CH2:26][O:27][C:22]=3[CH:21]=2)[CH2:42]1

Participants

7

Reactant 3

HCID 155702,5-DihydrofuranHCID 81531DiisopropylethylamineHCID 9549213Zelavespib

Product 2

HCID 21705897Ammonia methanolHCID 67115852HCID 67115852, compoundYield 37.6%

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), 2,5-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 (CH2Cl2:MeOH—NH3 (7N), 10:1, then hexane:EtOAc:CH2Cl2:MeOH—NH3 (7N), 2:1:2:0.5) to give 5.0 mg (19%) of DZ3-143. 1H NMR (500 MHz, CDCl3/MeOH-d4) δ 8.18 (s, 1H), 7.02 (s, 1H), 7.00 (s, 1H), 6.55 (m, 1H), 6.04 (s, 2H), 4.99 (m, 1H), 4.64-4.69 (m, 1H), 4.45 (m, 1H), 4.31 (t, J=6.8 Hz, 2H), 4.05 (dd, J=6.2, 9.2 Hz, 1H), 3.40 (m, 1H), 2.67 (t, J=6.4 Hz, 2H), 2.14 (m, 2H), 1.16 (d, J=6.1 Hz, 6H); HRMS (ESI) m/z [M+H]+ calcd. for C22H27N6O3S, 455.1865; found. 455.1862; HPLC: method A Rt=6.04, method B Rt=6.32.

Workup

  1. additionback filled with nitrogen
  2. customSolvent was removed under reduced pressure
  3. customthe resulting residue was purified by preparatory TLC two times (CH2Cl2

Sources & evidence

ORD record
ord-5e2c12ee386d46e0a89a6efdccbfcd29
Source dataset
uspto-grants-2016_05
Patent number
US09328114B2

Reaction notes

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