Dimethylformamide → (4-{3-[(2,3-difluoro-phenyl)-acetyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-cyclohex-3-enyl)-carbamic acid tert-butyl ester

HRID 269505Notes

Reaction equation

HRID 269505 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1C=N[O:12][C:13]=1[C:14]1[C:22]2[C:17](=[N:18][CH:19]=[C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:21]=2)[NH:16][CH:15]=1.C[N:30]([CH:32]=[O:33])C.[C:34]([O-])([O-])=O.[Na+].[Na+].ClC1C(Cl)=CC=CC=1[C:48]1C=N[O:51][C:52]=1[C:53]1C2C(=NC=CC=2)NC=1>CS(C)=O>[C:52]([O:51][C:32](=[O:33])[NH:30][CH:26]1[CH2:25][CH2:24][C:23]([C:20]2[CH:21]=[C:22]3[C:14]([C:13](=[O:12])[CH2:9][C:3]4[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=4[F:1])=[CH:15][NH:16][C:17]3=[N:18][CH:19]=2)=[CH:28][CH2:27]1)([CH3:53])([CH3:34])[CH3:48]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 1354836473-[4-(2,3-Dichloro-phenyl)-isoxazol-5-yl]-1H-pyrrolo[2, 3-b]pyridineHCID 1360665193-[4-(2,3-Difluoro-phenyl)-isoxazol-5-yl]-5-phenyl-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 59832239(4-{3-[(2,3-difluoro-phenyl)-acetyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-cyclohex-3-enyl)-carbamic acid tert-butyl esterYield 56%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of the above boronic ester (1.0 g, 2.5 mmol), trifluoro-methanesulfonic acid 4-tert-butoxycarbonylamino-cyclohex-1-enyl ester (690 mg, 2.0 mmol, prepared from (4-Oxo-cyclohexyl)-carbamic acid tert-butyl ester (Heterocycles 58 (2002) 471-504)) in a mixed solvent of DMF (15 ml) and DMSO (6 ml) was added aqueous 2.0M Na2CO3 (2 ml, 4 mmol) and PdCl2(PPh3) 2 The mixture was degassed and heated at 80° C. under Argon for 72 h, and then concentrated under high vacuum to remove DMF. The residue was suspended in aqueous NaHCO3, then filtered. The solid was purified for FC to give (4-{3-[(2,3-difluoro-phenyl)-acetyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-cyclohex-3-enyl)-carbamic acid tert-butyl ester as a white solid (530 mg) in 56% yield, LC-MS: m/e=468.4 (M+H), 466.4 (M−H). 1H-NMR (500 MHz, CDCl3) 13.41 (br.s, 1H), 9.23 (s, 1H), 8.44 (s, 1H), 8.38 (s, 1H), 7.09 (m, 3H), 6.24 (s, 1H), 4.56 (br. s, 1H), 4.32 (s, 2H), 3.90 (br.s, 1H), 2.63 (m, 3H), 2.13 (m, 2H), 1.28 (m, 1H), 1.49 (s, 9H).

Workup

  1. customwas degassed
  2. concentrationconcentrated under high vacuum
  3. customto remove DMF
  4. filtrationfiltered
  5. customThe solid was purified for FC

Sources & evidence

ORD record
ord-0176be0e41604a36ad25c6ce128846c9
Source dataset
uspto-grants-2008_11
Patent number
US07446199B2

Reaction notes

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