Sodium Hydroxide → [2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-(3-phenyl-allyl)-amine

HRID 885691Notes

Reaction equation

HRID 885691 reaction equation
[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[N:13]1[CH:21]=[C:20]2[C:15]([CH2:16][CH2:17][CH:18]([NH2:22])[CH2:19]2)=[N:14]1.[CH:23](=O)/[CH:24]=[CH:25]/[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[BH4-].[Na+].[OH-].[Na+]>CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C.CO>[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[N:13]1[CH:21]=[C:20]2[C:15]([CH2:16][CH2:17][CH:18]([NH:22][CH2:23][CH:24]=[CH:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:19]2)=[N:14]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 637511CinnamaldehydeHCID 4311764Sodium borohydrideHCID 595606482-(6-Methoxy-[1,5]naphthyridin-4-yl)4,5,6,7-tetrahydro-2H-indazol-5-ylamine

Product 1

HCID 68497225[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-(3-phenyl-allyl)-amineYield 50%

Reagents, catalysts & solvents 2

HCID 178460666HCID 178460666, compoundCatalystHCID 887MethanolSolvent

Procedure

To a suspension of 2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamine (50 mg, 0.17 mmol) and trans-cinnamaldehyde (20 mg, 0.15 mmol) in Ti(OiPr)4 (0.074 mL, 0.25 mmol) was added CH3OH (1 mL). The suspension was stirred for 3 h at RT. NaBH4 was added (9.0 mg, 0.24 mmol) and the reaction mixture was stirred for another 10 min, followed by the addition of 3 N NaOH (5 mL). The aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine (10 mL), dried (MgSO4), filtered, and concentrated. The crude was purified on SiO2 (0-5% CH3OH/CH2Cl2) to give 30 mg (50%) of the title compound as a clear oil. MS (ESI): exact mass calculated for C25H25N5O, 411.21; m/z found, 412.4 [M+H]+. 1H NMR (500 MHz, CDCl3): 9.10 (s, 1H), 8.76 (d, J=5.1, 1H), 8.25 (d, J=9.1, 1H), 8.15 (d, J=5.1, 2H), 7.37 (d, J=7.4, 2H), 7.30 (d, J=7.4, 2H), 7.23-7.20 (m, 1H), 7.18 (d, J=9.1, 1H), 6.57 (d, J=15.9, 1H), 6.34 (dt, J=15.9, 6.4, 1H), 4.10 (s, 3H), 3.55 (d, J=6.4, 2H), 3.15-3.11 (m, 1H), 3.06-3.01 (m, 1H), 2.99 (t, J=5.3, 1H), 2.86-2.80 (m, 1H), 2.53 (q, J=8.5, 1H), 2.17-2.15 (m, 1H), 1.88-1.81 (m, 1H).

Workup

  1. stirringthe reaction mixture was stirred for another 10 min
  2. extractionThe aqueous layer was extracted with EtOAc (3×20 mL)
  3. washThe combined organic layers were washed with brine (10 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude was purified on SiO2 (0-5% CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-f4b22e0ea4c947138bfd7ce8ca3794d3
Source dataset
uspto-grants-2012_08
Patent number
US08242275B2

Reaction notes

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