Triethylamine → HCID 75080606, compound

HRID 1093238Notes

Reaction equation

HRID 1093238 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH:9]=O)=[C:4](Cl)[N:3]=1.Cl.[CH2:13]([N:20]1[CH2:25][CH2:24][CH:23]([NH:26][NH2:27])[CH2:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CCN(CC)CC.Cl.[CH:36]12[O:43][CH:40]([CH2:41][CH2:42]1)[CH2:39][NH:38][CH2:37]2>C(Cl)Cl.C(O)C>[CH2:13]([N:20]1[CH2:21][CH2:22][CH:23]([N:26]2[C:6]3=[N:7][C:2]([Cl:1])=[N:3][C:4]([N:38]4[CH2:37][CH:36]5[O:43][CH:40]([CH2:41][CH2:42]5)[CH2:39]4)=[C:5]3[CH:9]=[N:27]2)[CH2:24][CH2:25]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 109327462,4,6-Trichloro-5-pyrimidinecarboxaldehydeHCID 219835368-Oxa-3-aza-bicyclo(3.2.1)octane hydrochlorideHCID 5460952983949-42-2

Product 1

HCID 75080606HCID 75080606, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2,4,6-trichloropyrimidine-5-carbaldehyde (26.82 mmol) in CH2Cl2 (225 mL) is cooled to −78° C. To this is added a suspension of 1-benzyl-4-hydrazinylpiperidine hydrochloride (26.82 mmol) in Et3N (160.9 mmol), CH2Cl2 (25 mL), and ethanol (15 mL). The solution is allowed to stir at this temperature for 5 minutes, then warmed to room temperature and stirred for an additional 30 minutes, then concentrated in vacuo at 30° C. This dichloride intermediate is dissolved in ethanol (225 mL) and a solution of 8-oxa-3-azabicyclo[3.2.1]octane hydrochloride (24.14 mmol) in Et3N (160.9 mmol) and ethanol (20 mL) is added. The mixture is stirred at room temperature for 1 hour, concentrated, and purified by column chromatography (0-4% methanol in CH2Cl2) provides 3-(1-(1-benzylpiperidin-4-yl)-6-chloro-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane. (66%, MS=439.3 (M+H))

Workup

  1. additionTo this is added
  2. stirringstirred for an additional 30 minutes
  3. concentrationconcentrated in vacuo at 30° C
  4. dissolutionThis dichloride intermediate is dissolved in ethanol (225 mL)
  5. stirringThe mixture is stirred at room temperature for 1 hour
  6. concentrationconcentrated
  7. custompurified by column chromatography (0-4% methanol in CH2Cl2)

Sources & evidence

ORD record
ord-7a05580fb08046cf9dc743fb6708203b
Source dataset
uspto-grants-2012_03
Patent number
US08129371B2

Reaction notes

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