Dichloromethane → HCID 11518602, compound

HRID 1365896Notes

Reaction equation

HRID 1365896 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([NH:16][C:17]2[CH:18]=[C:19]([C:23]3[N:28]=[C:27](Cl)[CH:26]=[C:25]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)[N:24]=3)[CH:20]=[CH:21][CH:22]=2)=[O:15])[CH2:10][CH2:9]1)=O)(C)(C)C.[OH:36][CH2:37][C:38]1[S:42][C:41](B(O)O)=[CH:40][CH:39]=1.[F-].[Cs+].C(Cl)Cl>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CO>[OH:36][CH2:37][C:38]1[S:42][C:41]([C:27]2[CH:26]=[C:25]([N:30]3[CH2:31][CH2:32][O:33][CH2:34][CH2:35]3)[N:24]=[C:23]([C:19]3[CH:20]=[CH:21][CH:22]=[C:17]([NH:16][C:14]([CH:11]4[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)=[O:15])[CH:18]=3)[N:28]=2)=[CH:40][CH:39]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 25953Cesium fluorideHCID 43742655-Hydroxymethylthiophene-2-boronic acidHCID 86630889HCID 86630889, compound

Product 1

HCID 11518602HCID 11518602, compoundYield 29.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-[3-(1-tert-butoxycarbonylpiperidin-4-ylcarbonylamino)phenyl]-4-chloro-6-morpholinopyrimidine (0.054 g), 5-hydroxymethylthien-2-ylboronic acid (0.021 g), caesium fluoride (0.046 g), a [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) 1:1 complex with methylene chloride (3 mg), and methanol (2 ml) was stirred and heated to 120° C. using microwave radiation for 20 minutes under an atmosphere of nitrogen in a sealed glass tube. The resultant reaction mixture was evaporated and the residue was partitioned between methylene chloride and water. The organic solution was dried over magnesium sulphate and evaporated. The residue was purified by column chromatography on silica using an increasingly polar gradient of 0% to 5% methanol in methylene chloride as eluent. There was thus obtained 2-[3-(N-tert-butoxycarbonylpiperidin-4-ylcarbonylamino)phenyl]-4-(5-hydroxymethylthien-2-yl)-6-morpholinopyrimidine as a gum. Trifluoroacetic acid (2 ml) was added to the material so obtained and the mixture was stirred at ambient temperature for 30 minutes. The mixture was evaporated and the residue was purified by HPLC using a Waters ‘Xterra’ preparative reversed-phase column (5 microns silica, 19 mm diameter, 100 mm length) using decreasingly polar mixtures of water (containing 1% of a concentrated (d=0.88) aqueous ammonium hydroxide solution) and acetonitrile as eluent. There was thus obtained the title compound as a solid (0.015 g); NMR Spectrum: (DMSO-d6) 1.55-1.66 (m, 2H), 3.04 (d, 2H), 3.77 (d, 8H), 4.69 (d, 2H), 5.57 (t, 1H), 7.05 (d, 1H), 7.19 (s, 1H), 7.4 (t, 1H), 7.9-7.95 (m, 2H), 8.07 (d, 1H), 8.48 (s, 1H), 10.01 (s, 1H); Mass Spectrum: M+H+480.

Workup

  1. customfor 20 minutes
  2. customThe resultant reaction mixture
  3. customwas evaporated
  4. customthe residue was partitioned between methylene chloride and water
  5. dry with materialThe organic solution was dried over magnesium sulphate
  6. customevaporated
  7. customThe residue was purified by column chromatography on silica using an increasingly polar gradient of 0% to 5% methanol in methylene chloride as eluent
  8. additionTrifluoroacetic acid (2 ml) was added to the material
  9. customso obtained
  10. customThe mixture was evaporated
  11. customthe residue was purified by HPLC
  12. additioncontaining 1% of
  13. concentrationa concentrated (d=0.88) aqueous ammonium hydroxide solution) and acetonitrile as eluent

Sources & evidence

ORD record
ord-e715e942296b4488a43d9cb376d1f29c
Source dataset
uspto-grants-2011_02
Patent number
US07893063B2

Reaction notes

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