tert-Butyl 4-sulfanylpiperidine-1-carboxylate → HCID 58266610, compound

HRID 1888522Notes

Reaction equation

HRID 1888522 reaction equation
Br[C:2]1[C:7]2[C:8]3[CH:22]=[C:21]([C:23]4[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=4)[CH:20]=[N:19][C:9]=3[N:10]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:6]=2[CH:5]=[N:4][C:3]=1[C:29]#[N:30].[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][CH:41]([SH:44])[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].CC(C)([O-])C.[Na+]>C(COC)OC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][CH:41]([S:44][C:2]2[C:7]3[C:8]4[CH:22]=[C:21]([C:23]5[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=5)[CH:20]=[N:19][C:9]=4[N:10]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:6]=3[CH:5]=[N:4][C:3]=2[C:29]#[N:30])[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]

Participants

6

Reactant 3

HCID 21906090tert-Butyl 4-sulfanylpiperidine-1-carboxylateHCID 23676156Sodium t-butoxideHCID 58266535HCID 58266535, compound

Product 1

HCID 58266610HCID 58266610, compoundYield 68.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
100 °C

Procedure

To a degassed suspension of 5-bromo-3-(1-methyl-1H-pyrazol-4-yl)-9-(2-trimethylsilanylethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (120 mg, 0.25 mmol), 4-mercaptopiperidine-1-carboxylic acid tert-butyl ester (54 mg, 0.25 mmol) and sodium tert-butoxide (26.4 mg, 0.28 mmol) in dimethoxyethane (0.4 mL) in a sealed 5 ml microwave vial was added a degassed solution of palladium(II) acetate (2.2 mg, 0.01 mmol) and (R)-(−)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyldi-tert-butylphosphine (5.5 mg, 0.01 mmol) in dimethoxyethane (1.0 mL). The reaction mixture was heated at 100° C. for 22 h then cooled to ambient temperature and concentrated in vacuo. The resultant residue was adsorbed onto HM-N then purified by flash chromatography (silica, 50 g column, Si-SPE, 0-10% (2M ammonia in MeOH) in DCM) to afford the title compound as a yellow solid (106 mg, 68%). 1H NMR (DMSO-D6, 300 MHz): 9.33 (s, 1H), 9.11-9.06 (m, 2H), 8.35 (s, 1H), 8.05-8.01 (m, 1H), 6.05 (s, 2H), 3.93 (s, 3H), 3.86-3.73 (m, 2H), 3.64-3.53 (m, 2H), 2.97-2.78 (m, 3H), 1.97-1.83 (m, 2H), 1.64-1.45 (m, 2H), 1.35 (s, 9H), 0.87-0.78 (m, 2H), −0.17 (s, 9H).

Workup

  1. temperaturethen cooled to ambient temperature
  2. concentrationconcentrated in vacuo
  3. customthen purified by flash chromatography (silica, 50 g column, Si-SPE, 0-10% (2M ammonia in MeOH) in DCM)

Sources & evidence

ORD record
ord-68a774a6eaa8492691783368e84a1e28
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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