Dimethylformamide → HCID 86591494, compound

HRID 585524Notes

Reaction equation

HRID 585524 reaction equation
Br[C:2]1[S:3][C:4]2[N:5]3[C:9]([C:10]([NH:14][CH2:15][CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[N:11][C:12]=2[CH:13]=1)=[N:8][CH:7]=[C:6]3[CH3:25].C(N(CC)CC)C.[CH3:33][C:34](C)([C:36]#[CH:37])C.CN(C)[CH:41]=[O:42]>[Cu]I>[OH:42][CH:41]([C:2]1[S:3][C:4]2[N:5]3[C:9]([C:10]([NH:14][CH2:15][CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[N:11][C:12]=2[CH:13]=1)=[N:8][CH:7]=[C:6]3[CH3:25])[CH2:37][CH2:36][C:34]#[CH:33]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 135123,3-Dimethyl-1-butyneHCID 22336989HCID 22336989, compound

Product 1

HCID 86591494HCID 86591494, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
80 °C

Procedure

A solution of N-(2-bromo-8-methyl-1-thia-4,6,8a-triaza-as-indacen-5-yl)-N-(2-tert-butoxycarbonylaminoethyl)-amine (0.030 g, 0.070 mmol) in N,N-dimethylformamide (1 mL) was added copper(I) iodide (10.5 mgs), triethylamine (0.05 mL) and 2,2-dimethyl-but-3-yne (200 μL, 3.65 mmol). Argon was bubbled in the solution, then palladium(II) triphenylphosphine (13.8 mgs) was added and the mixture was stirred at 80° C. for 2 hours. The mixture was filtered on celite and the solvent was evaporated. The residue was purified by silica gel chromatography (50% ethyl acetate in hexane) to give N-(2-(hydroxy-pentyn-5-yl)-8-methyl-1-thia-4,6,8a-triaza-as-indacen-5-yl)-N-(2-tert-butoxycarbonylaminoethyl)-amine (0.021 g, 70%). This compound was dissolved in dichloromethane (1 mL) and treated with trifluoroacetic acid (0.2 mL) for 45 minutes. The solvents were evaporated and the residue was dissolved in methanol and treated with MP-carbonate resin. This mixture was stirred at room temperature for 2 hours, then filtered. The resin was washed with methanol and the filtrate was evaporated to give Compound 393 (0.014 g, 87%). NMR (DMSO-d6, 400 MHz) δ: 7.36 (2H, s), 7.27 (1H, s), 7.25 (1H, s), 3.51 (2H, q, J=5.6 Hz), 2.87 (2H, m), 2.65 (3H, s), 1.24 (9H, s). LRMS (ESI, m/z, M+H+) 327. HRMS for C17H21N5S calcd: 327.1518, found: 327.1516.

Workup

  1. customArgon was bubbled in the solution
  2. additionpalladium(II) triphenylphosphine (13.8 mgs) was added
  3. filtrationThe mixture was filtered on celite
  4. customthe solvent was evaporated
  5. customThe residue was purified by silica gel chromatography (50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-b23f4f4f781c4c8bb29d9feaa4122d38
Source dataset
uspto-grants-2005_08
Patent number
US06933294B2

Reaction notes

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