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

HRID 1257592Notes

Reaction equation

HRID 1257592 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.[NH2:23][CH:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]1.C(N(C(C)C)CC)(C)C>CC(O)C>[C:33]([O:32][C:30]([N:27]1[CH2:28][CH2:29][CH:24]([NH:23][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)[CH2:25][CH2:26]1)=[O:31])([CH3:36])([CH3:34])[CH3:35]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 583947741-(benzenesulfonyl)-4-chloro-5-nitro-1H-pyrrolo(2,3-b)pyridine

Product 1

HCID 673440274-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridine-4-ylamino)-piperidine-1-carboxylic acid tert-butyl esterYield 58.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-benzenesulfonyl-4-chloro-5-nitro-1H-pyrrolo[2,3-b]pyridine (15.6 g, 46.2 mmol), 4-amino-1-Boc-piperidine (10.18 g, 50.8 mmol), diisopropylethylamine (20.9 ml, 120 mmol) in propan-2-ol (200 ml) was heated at 80° C. for 11 h. The mixture was then cooled to 25° C. and was concentrated under reduced pressure. The yellow-orange residue was partitioned between water (150 ml) and CH2Cl2 (2×200 ml). The combined organic layers were dried over MgSO4, filtered, and the filtrate was concentrated under reduced pressure to afford crude 4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (26.4 g, 114%) as a yellow-orange foam. A portion of this material (11.2 g) was used in the next step below. The remaining material was purified by column chromatography on silica gel (gradient: 0 to 70% EtOAc in heptanes) to give the title compound (13.49 g) as a yellow solid. LCMS (Method G, ESI): RT=1.24 min, m+H=502.3; 1H NMR (400 MHz, CDCl3) δ 9.10 (s, 1H), 9.08 (s, 1H), 8.19 (d, J=8.0 Hz, 2H), 7.63 (dd, J=8.1, 5.9 Hz, 2H), 7.52 (t, J=7.8 Hz, 2H), 6.70 (d, J=4.2 Hz, 1H), 4.22-4.07 (m, 1H), 4.01 (d, J=13.3 Hz, 2H), 3.12 (t, J=11.3 Hz, 2H), 2.17-2.04 (m, 2H), 1.69-1.58 (m, 2H), 1.47 (s, 9H).

Workup

  1. temperatureThe mixture was then cooled to 25° C.
  2. concentrationwas concentrated under reduced pressure
  3. customThe yellow-orange residue was partitioned between water (150 ml) and CH2Cl2 (2×200 ml)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customto afford crude 4-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (26.4 g, 114%) as a yellow-orange foam
  8. customThe remaining material was purified by column chromatography on silica gel (gradient: 0 to 70% EtOAc in heptanes)

Sources & evidence

ORD record
ord-7c4e342d2b4b4e61967224ef1b8d0ddd
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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