Acetic Acid → 3-(1,3-Benzoxazol-2-yl)-5-[1-(1-methyl-4-piperidyl)pyrazol-4-yl]pyridin-2-amine

HRID 908370Notes

Reaction equation

HRID 908370 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:27])=[N:12][CH:13]=[C:14]([C:16]2[CH:17]=[N:18][N:19]([CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[CH:20]=2)[CH:15]=1.[C:28](O)(=O)C.C=O.C([BH3-])#N.[Na+]>CO>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:27])=[N:12][CH:13]=[C:14]([C:16]2[CH:17]=[N:18][N:19]([CH:21]3[CH2:22][CH2:23][N:24]([CH3:28])[CH2:25][CH2:26]3)[CH:20]=2)[CH:15]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 441601373-(1,3-Benzoxazol-2-yl)-5-[1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine

Product 1

HCID 425993593-(1,3-Benzoxazol-2-yl)-5-[1-(1-methyl-4-piperidyl)pyrazol-4-yl]pyridin-2-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3-(1,3-Benzoxazol-2-yl)-5-[1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine (1.8 g) was added to a mixture of acetic acid (2.86 μL) and 37% aqueous formaldehyde (0.583 ml) dissolved in methanol (40 ml) and the resulting solution was stirred for 15 minutes. Sodium cyanoborohydride (0.377 g) was then added and the mixture was stirred for a further 3 hours. The reaction mixture was concentrated to dryness and diluted with DCM and purified by flash chromatography on silica gel (eluting with a gradient of 5 to 10% 7N methanolic ammonia in dichloromethane). The solvent was evaporated to dryness and there was thus obtained 3-(1,3-benzoxazol-2-yl)-5-[1-(1-methyl-4-piperidyl)pyrazol-4-yl]pyridin-2-amine (1.180 g); Mass Spectrum: M+H+ 375.1; RT 1.73 min; NMR Spectrum: (DMSOd6) 8.53 (d, 1H), 8.44 (d, 1H), 8.32 (d, 1H), 7.92 (d, 1H), 7.85 (m, 1H), 7.80 (m, 1H), 7.64 (br s, 2H), 7.46 (m, 2H), 4.13 (m, 1H), 2.88 (br m, 2H), 2.23 (s, 3H), 2.04 (m, 6H).

Workup

  1. stirringthe mixture was stirred for a further 3 hours
  2. concentrationThe reaction mixture was concentrated to dryness
  3. additiondiluted with DCM
  4. custompurified by flash chromatography on silica gel (
  5. washeluting with a gradient of 5 to 10% 7N methanolic ammonia in dichloromethane)
  6. customThe solvent was evaporated to dryness and there
  7. customRT 1.73 min

Sources & evidence

ORD record
ord-f78e1364603a4b619a798ee582e0fbe8
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

Loading…