Butanedione → N-(2,2-dimethoxyethyl)-2-(2-pyrrolidin-1-ylethyl)-2H-indazol-5-amine

HRID 1825842Notes

Reaction equation

HRID 1825842 reaction equation
[N:1]1([CH2:6][CH2:7][N:8]2[CH:16]=[C:15]3[C:10]([CH:11]=[CH:12][C:13]([NH2:17])=[CH:14]3)=[N:9]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CC(=O)[C:20](C)=[O:21].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[CH2:38]1[CH2:42][O:41][CH2:40]C1>CCOCC>[CH3:20][O:21][CH:42]([O:41][CH3:40])[CH2:38][NH:17][C:13]1[CH:12]=[CH:11][C:10]2[C:15](=[CH:16][N:8]([CH2:7][CH2:6][N:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[N:9]=2)[CH:14]=1

Participants

6

Reactant 4

HCID 650ButanedioneHCID 8028Tetrahydrofuran2×HCID 5049666Sodium triacetoxyborohydride2×HCID 112069772-(2-pyrrolidin-1-ylethyl)-2H-indazol-5-amine

Product 1

HCID 22138916N-(2,2-dimethoxyethyl)-2-(2-pyrrolidin-1-ylethyl)-2H-indazol-5-amine

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of 2-(2-pyrrolidin-1-ylethyl)-2H-indazol-5-amine (1.14 g, 0.497 mmol) in 62 mL of dry THF was added 2.04 mL of dimethyl glyoxal in ether (45% glyoxal by weight). A slurry of NaBH(OAc)3 (1.66 g, 7.83 mmol) in THF (10 mL) was slowly added via addition funnel over 60 minutes, and the mixture stirred at room temperature for 12 hours, after which an additional equivalent of NaBH(OAc)3 was added. After an additional 12 hours, the mixture was quenched with saturated NaHCO3, filtered, and the solvents removed under reduced pressure. The residue was purified via column chromatography eluting with 5–15% Et3N in EtOAc to provide 650 mg (2.04 mmol) of the title compound. 1H NMR (300 MHz, DMSO-D6) δ ppm 1.55–1.73 (m, 4 H) 2.39–2.49 (m, 4 H) 2.85–2.96 (m, 2 H) 3.05–3.20 (m, 2 H) 3.28–3.33 (m, 6 H) 4.31–4.45 (m, 2 H) 4.48–4.61 (m, 1 H) 5.14–5.32 (m, 1 H) 6.37–6.50 (m, 1 H) 6.74–6.91 (m, 1 H) 7.21–7.42 (m, 1 H) 7.83–8.02 (m, 1 H); MS (ESI) m/z 319 [M+H]+.

Workup

  1. waitAfter an additional 12 hours
  2. customthe mixture was quenched with saturated NaHCO3
  3. filtrationfiltered
  4. customthe solvents removed under reduced pressure
  5. customThe residue was purified via column chromatography
  6. washeluting with 5–15% Et3N in EtOAc

Sources & evidence

ORD record
ord-ce014252c8e94e4dbd436756db6da13e
Source dataset
uspto-grants-2006_05
Patent number
US07049307B2

Reaction notes

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