Ammonia → 2-Pyridinamine, 3-(2-benzoxazolyl)-5-[3-methyl-1-(1-methyl-4-piperidinyl)-1H-pyrazol-4-yl]-

HRID 908386Notes

Reaction equation

HRID 908386 reaction equation
[CH2:1]=O.[O:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[C:4]1[C:12]1[C:13]([NH2:30])=[N:14][CH:15]=[C:16]([C:18]2[C:19]([CH3:29])=[N:20][N:21]([CH:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)[CH:22]=2)[CH:17]=1.[Na].N>CO.ClCCl>[O:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[C:4]1[C:12]1[C:13]([NH2:30])=[N:14][CH:15]=[C:16]([C:18]2[C:19]([CH3:29])=[N:20][N:21]([CH:23]3[CH2:24][CH2:25][N:26]([CH3:1])[CH2:27][CH2:28]3)[CH:22]=2)[CH:17]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 712FormaldehydeHCID 5360545SodiumHCID 425993613-(1,3-Benzoxazol-2-yl)-5-[3-methyl-1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine

Product 1

HCID 425996032-Pyridinamine, 3-(2-benzoxazolyl)-5-[3-methyl-1-(1-methyl-4-piperidinyl)-1H-pyrazol-4-yl]-

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

37% Aqueous formaldehyde (0.042 ml) at 0° C. was added to a stirred solution of 3-(1,3-benzoxazol-2-yl)-5-[3-methyl-1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine (178 mg) dissolved in methanol (2 ml) and dichloromethane (2 ml) over a period of 5 minutes under argon. The resulting solution was stirred at 0° C. for 5 minutes. Then sodium triacetoxyhydroborate (121 mg) was added and the mixture was stirred for 5 minutes at 25° C. A solution of ammonia in methanol 7N (2 ml) was added and the mixture was adsorbed on silica gel. The crude product was purified by flash chromatography on silica gel eluting with 5% methanolic ammonia (7 N) in dichloromethane. The solvent was evaporated to dryness, then the resulting solid was stirred in acetonitrile overnight, filtered and dried to afford 3-(1,3-benzoxazol-2-yl)-5-[3-methyl-1-(1-methyl-4-piperidyl)pyrazol-4-yl]pyridin-2-amine (125 mg) as a solid; NMR Spectrum: (DMSOd6) 1.88-2.11 (m, 6H), 2.21 (s, 3H), 2.33 (s, 3H), 2.81-2.93 (m, 2H), 3.97-4.11 (m, 1H), 7.38-7.50 (m, 2H), 7.65 (bs, 2H), 7.79 (d, 1H), 7.84 (d, 1H), 8.07 (s, 1H), 8.28 (s, 1H), 8.35 (s, 1H); Mass spectrum: M+H+: 389

Workup

  1. stirringthe mixture was stirred for 5 minutes at 25° C
  2. customThe crude product was purified by flash chromatography on silica gel eluting with 5% methanolic ammonia (7 N) in dichloromethane
  3. customThe solvent was evaporated to dryness
  4. stirringthe resulting solid was stirred in acetonitrile overnight
  5. filtrationfiltered
  6. customdried

Sources & evidence

ORD record
ord-9bc25e8c961c4169980d0a4462fedb5e
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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