2-Aminopyrimidine → HCID 16069045, compound

HRID 2047570Notes

Reaction equation

HRID 2047570 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:5]2[N:6]=[C:7]([C@H:9]3[CH2:12][C@H:11]([N:13]4[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]4)[CH2:10]3)[S:8][C:4]=2[CH:3]=1.[NH2:21][C:22]1[N:27]=[CH:26][CH:25]=[CH:24][N:23]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[N:13]1([CH:11]2[CH2:12][CH:9]([C:7]3[S:8][C:4]4[CH:3]=[C:2]([NH:21][C:22]5[N:27]=[CH:26][CH:25]=[CH:24][N:23]=5)[CH:20]=[CH:19][C:5]=4[N:6]=3)[CH2:10]2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

8

Reactant 4

HCID 79782-AminopyrimidineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 178419317HCID 178419317, compound

Product 1

HCID 16069045HCID 16069045, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
145 °C

Procedure

The product of Example 44A (trans-6-bromo-2-(3-piperidin-1-ylcyclobutyl)-1,3-benzothiazole) (100 mg, 0.285 mmole), 2-aminopyrimidine (35 mg, 0.368 mmole), tris(dibenzylideneacetone)dipalladium (0) (10.4 mg, 0.011 mmole), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP, 14 mg, 0.022 mmole) and sodium tert-butoxide (38 mg, 0.400 mmole) were charged in a tube and sealed. The tube was placed on high vacuum for 2 hours and refilled with nitrogen. Toluene (2 mL) was added and the reaction vessel was placed in a microwave reactor and heated at 145° C. for 15 minutes. After cooling to room temperature, the mixture was diluted with water and extracted three times with dichloromethane. The combined organic layers were concentrated under reduced pressure and the crude product was purified by column chromatography (0.4% ammonium hydroxide and 4% methanol in dichloromethane). The product collected was a mixture of cis and trans isomers (98 mg). 1H NMR (400 MHz, CDCl3) δ ppm 8.42-8.49 (m, 3H) 7.89 (d, 2H) 7.37-7.46 (m, 2H) 6.75 (t, J=4.76 Hz, 1H) 3.75-3.86 (m, 0.6H) 3.48-3.62 (m, 0.4H) 3.03-3.17 (m, 0.6H) 2.73-2.84 (m, 0.4H) 2.48-2.72 (m, 4H) 2.21-2.42 (m, 4H) 1.55-1.66 (m, 4H) 1.41-1.51 (m, 2H). MS: (M+H)+=366.

Workup

  1. customsealed
  2. additionrefilled with nitrogen
  3. customthe reaction vessel was placed in a microwave reactor
  4. temperatureAfter cooling to room temperature
  5. extractionextracted three times with dichloromethane
  6. concentrationThe combined organic layers were concentrated under reduced pressure
  7. customthe crude product was purified by column chromatography (0.4% ammonium hydroxide and 4% methanol in dichloromethane)
  8. customThe product collected
  9. additiona mixture of cis and trans isomers (98 mg)

Sources & evidence

ORD record
ord-fdb3e2bd60954a0eb7a1d6cb08bab4e9
Source dataset
uspto-grants-2013_11
Patent number
US08592467B2

Reaction notes

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