Triethylamine → HCID 86684724, compound

HRID 339226Notes

Reaction equation

HRID 339226 reaction equation
I[C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C@@H:10]([O:15][CH2:16][C:17]2[C:18]([NH2:32])=[N:19][C:20](=[O:31])[N:21]([CH:30]=2)[C@@H:22]2[O:29][C@H:26]([CH2:27][OH:28])[C@@H:24]([OH:25])[CH2:23]2)[C:11]([CH3:14])([CH3:13])[CH3:12])=[C:4]([N+:33]([O-:35])=[O:34])[CH:3]=1.[CH2:36]([N-:39][C:40](=[O:45])[C:41]([F:44])([F:43])[F:42])[C:37]#[CH:38].CCN(CC)CC>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I>[CH3:9][O:8][C:7]1[C:2]([C:38]#[C:37][CH2:36][NH:39][C:40](=[O:45])[C:41]([F:44])([F:43])[F:42])=[CH:3][C:4]([N+:33]([O-:35])=[O:34])=[C:5]([C@@H:10]([O:15][CH2:16][C:17]2[C:18]([NH2:32])=[N:19][C:20](=[O:31])[N:21]([CH:30]=2)[C@@H:22]2[O:29][C@H:26]([CH2:27][OH:28])[C@@H:24]([OH:25])[CH2:23]2)[C:11]([CH3:13])([CH3:14])[CH3:12])[CH:6]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 86684722HCID 86684722, compoundHCID 178457782HCID 178457782, compound

Product 1

HCID 86684724HCID 86684724, compoundYield 91.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of compound 66 (245 mg, 0.4 mmol), N-propargyltrifluoroacetylamide (603 mg, 4.0 mmol), tetrakis(triphenylphosphine)-palladium(0) (92 mg, 0.8 mmol), CuI (30 mg, 0.16 mmol), and Et3N (240 μL, 1.7 mmol) in anhydrous DMF (5.0 mL) was stirred at 50° C. for 12 hours. The mixture was concentrated in vacuo and purified by silica gel column chromatography to yield 5-{(S)-1-[5-methoxy-4-(3-trifluoroacetamido-1-propynyl)-2-nitrophenyl]-2,2-dimethyl-propyloxy}methyl-2′-deoxycytidine 67 (230 mg, 91%). 1H NMR (400 MHz, MeOD-d4): δ 7.98 (s, 1H, Ph-H), 7.92 (s, 1H, H-6), 7.19 (s, 1H, Ph-H), 6.15 (t, 1H, J=6.4 Hz, H-1′), 5.21 (s, 1H, Ph-CH), 4.41 (d, 1H, J=13.2 Hz, 5-CH2a), 4.33 (m, 3H, H-3′ and CH2), 4.27 (d, 1H, J=13.2 Hz, 5-CH2b), 3.96 (s, 3 H, OCH3), 3.88 (m, 1H, H-4′), 3.72 (m, 2H, H-5′), 2.30 (m, 1H, H-2′a), 2.12 (m, 1H, H-2′b), 0.84 (s, 9H, C(CH3)3).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-a846c3e1bf6c48b3bdaa14a8bfc96b82
Source dataset
uspto-grants-2014_11
Patent number
US08889860B2

Reaction notes

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