Diisopropylethylamine → 4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-4-methyl-piperidine-1-carboxylic acid tert-butyl ester

HRID 1257629Notes

Reaction equation

HRID 1257629 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[C:18](Cl)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][C:33]([NH2:37])([CH3:36])[CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].C(N(C(C)C)CC)(C)C>CC(O)C>[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][C:33]([NH:37][C:18]2[C:17]([N+:20]([O-:22])=[O:21])=[CH:16][N:15]=[C:14]3[N:10]([S:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)(=[O:9])=[O:8])[CH:11]=[CH:12][C:13]=23)([CH3:36])[CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:24])[CH3:25]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 11310432tert-Butyl 4-amino-4-methylpiperidine-1-carboxylateHCID 583947741-(benzenesulfonyl)-4-chloro-5-nitro-1H-pyrrolo(2,3-b)pyridine

Product 1

HCID 673449584-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-4-methyl-piperidine-1-carboxylic acid tert-butyl esterYield 80.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 1-benzenesulfonyl-4-chloro-5-nitro-1H-pyrrolo[2,3-b]pyridine (750 mg, 2.20 mmol), 4-amino-4-methyl-piperidine-1-carboxylic acid tert-butyl ester (525 mg, 2.50 mmol) and diisopropylethylamine (1.36 mL, 7.80 mmol) in propan-2-ol (30 mL) was heated to reflux for 65 hours. The cooled reaction mixture was filtered and the yellow solid further purified by column chromatography on silica gel (gradient: 0 to 30% ethyl acetate in cyclohexane) to afford 910 mg (79%) of 4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-4-methyl-piperidine-1-carboxylic acid tert-butyl ester. LCMS (Method H, ESI): RT=4.35 min, m+H=516.2; 1H NMR (400 MHz, DMSO) δ: 9.42 (s, 1H), 8.95 (s, 1H), 8.15 (dd, 2H), 7.84-7.76 (m, 2H), 7.66 (m, 2H), 7.06 (d, 1H), 3.57 (m, 2H), 3.23-3.08 (m, 1H), 2.09 (d, 2H), 1.80 (m, 2H), 1.57 (s, 3H), 1.39 (s, 9H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 65 hours
  3. customThe cooled reaction mixture
  4. filtrationwas filtered
  5. customthe yellow solid further purified by column chromatography on silica gel (gradient: 0 to 30% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-ef180e06424445cda2a8df729bb85e9d
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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