Trifluoroacetic acid → 3-(1,3-Benzoxazol-2-yl)-5-[1-(4-piperidyl)triazol-4-yl]pyridin-2-amine

HRID 908437Notes

Reaction equation

HRID 908437 reaction equation
C(O)(C(F)(F)F)=O.[NH2:8][C:9]1[N:14]=[CH:13][C:12]([C:15]2[N:16]=[N:17][N:18]([CH:20]3[CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH2:21]3)[CH:19]=2)=[CH:11][C:10]=1[C:33]1[O:34][C:35]2[CH:41]=[CH:40][CH:39]=[CH:38][C:36]=2[N:37]=1>ClCCl>[O:34]1[C:35]2[CH:41]=[CH:40][CH:39]=[CH:38][C:36]=2[N:37]=[C:33]1[C:10]1[C:9]([NH2:8])=[N:14][CH:13]=[C:12]([C:15]2[N:16]=[N:17][N:18]([CH:20]3[CH2:21][CH2:22][NH:23][CH2:24][CH2:25]3)[CH:19]=2)[CH:11]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67388898Tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]triazol-1-yl]piperidine-1-carboxylate

Product 1

HCID 576870133-(1,3-Benzoxazol-2-yl)-5-[1-(4-piperidyl)triazol-4-yl]pyridin-2-amineYield 99.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (0.771 ml) was added to a stirred suspension of tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]triazol-1-yl]piperidine-1-carboxylate (231 mg) dissolved in dichloromethane (5 ml) at room temperature. The resulting solution was stirred for 2 hours. Excess TFA was removed by azeotropic concentration with toluene. The residue was taken off with dichloromethane-methanol and treated with methanolic ammonia (7 M). The mixture was concentrated to dryness and the resulting solid was triturated with diethyl ether. The resultant solid was collected by filtration, washed with diethyl ether followed by petroleum ether and dried under vacuum at 60° C. to give 3-(1,3-benzoxazol-2-yl)-5-[1-(4-piperidyl)triazol-4-yl]pyridin-2-amine (180 mg) as a solid; NMR Spectrum: (DMSOd6+TFAd) 2.20-2.32 (m, 2H), 2.38-2.48 (m, 2H), 3.7-3.30 (m, 2H), 3.47-3.58 (m, 2H), 4.92-5.02 (m, 1H), 7.54 (ddd, 1H), 7.59 (ddd, 1H), 7.90 (d, 1H), 7.95 (dd, 1H), 8.84 (d, 1H), 8.96 (s, 1H), 9.24 (d, 1H); Mass spectrum: M+H+: 362

Workup

  1. customExcess TFA was removed by azeotropic concentration with toluene
  2. additiontreated with methanolic ammonia (7 M)
  3. concentrationThe mixture was concentrated to dryness
  4. customthe resulting solid was triturated with diethyl ether
  5. filtrationThe resultant solid was collected by filtration
  6. washwashed with diethyl ether
  7. customdried under vacuum at 60° C.

Sources & evidence

ORD record
ord-52d3af5a1537446481b64cbef5862960
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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