Methoxyacetyl chloride → 1-(4-(4-(6-amino-5-(benzo[d]oxazol-2-yl)pyridin-3-yl)-1H-pyrazol-1-yl)piperidin-1-yl)-2-methoxyethanone tetrahydrochloride

HRID 908411Notes

Reaction equation

HRID 908411 reaction equation
[CH3:1][O:2][CH2:3][C:4](Cl)=[O:5].[O:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[C:16]1[C:17]([NH2:33])=[N:18][CH:19]=[C:20]([C:22]2[CH:23]=[N:24][N:25]([CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)[CH:26]=2)[CH:21]=1.C(N(C(C)C)C(C)C)C1C=CC=CC=1>ClCCl.C1COCC1>[NH2:33][C:17]1[N:18]=[CH:19][C:20]([C:22]2[CH:23]=[N:24][N:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:4](=[O:5])[CH2:3][O:2][CH3:1])[CH2:29][CH2:28]3)[CH:26]=2)=[CH:21][C:16]=1[C:8]1[O:7][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=1

Participants

6

Reactant 3

HCID 96623Methoxyacetyl chlorideHCID 4578032BenzyldiisopropylamineHCID 441601373-(1,3-Benzoxazol-2-yl)-5-[1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine

Product 1

HCID 497984811-(4-(4-(6-amino-5-(benzo[d]oxazol-2-yl)pyridin-3-yl)-1H-pyrazol-1-yl)piperidin-1-yl)-2-methoxyethanone tetrahydrochloride

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-methoxyacetyl chloride (0.033 ml) was added in one portion to a stirred ice-cooled suspension of 3-(1,3-benzoxazol-2-yl)-5-[1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine (100 mg) and N-benzyl-N-isopropyl-propan-2-amine on polystyrene (185 mg, 3 mmol/g) in dichloromethane (5 ml) and THF (5 ml). The resulting suspension was stirred at room temperature for 2 hours. The resin was filtered, rinsed with dichloromethane/methanol. The filtrate was concentrated to dryness. The crude product was purified by flash chromatography on silica gel eluting with 0 to 4% methanol in dichloromethane. After evaporation of the solvants, the resulting solid was triturated in acetonitrile to give the title compound (79 mg). NMR Spectrum: (CDCl3): 1.97-2.11 (m, 2H), 2.22-2.35 (m, 2H), 2.80-2.91 (m, 1H), 3.17-3.29 (m, 1H), 3.46 (s, 3H), 4.06-4.23 (m, 3H), 4.38-4.47 (m, 1H), 4.69-4.80 (m, 1H), 7.08 (bs, 2H), 7.35-7.42 (m, 2H), 7.58-7.63 (m, 1H), 7.69 (s, 1H), 7.73-7.78 (m, 1H), 7.80 (s, 1H), 8.35 (d, 1H), 8.41 (d, 1H); Mass spectrum: M+H+ 433.

Workup

  1. temperaturecooled
  2. filtrationThe resin was filtered
  3. washrinsed with dichloromethane/methanol
  4. concentrationThe filtrate was concentrated to dryness
  5. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 4% methanol in dichloromethane
  6. customAfter evaporation of the solvants
  7. customthe resulting solid was triturated in acetonitrile

Sources & evidence

ORD record
ord-8b058125c78243049b42b8d01153f86b
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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