Dimethylformamide → HCID 59605806, compound

HRID 1945960Notes

Reaction equation

HRID 1945960 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][N:13]3[CH2:16][CH:15]([CH:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[CH2:14]3)[N:8]2[CH3:11])=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:3]=1.[NH:29]1[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[N:31]=[C:30]1CN.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:80][N:81](C=O)C>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]>[CH3:80][NH:81][C:30]1[N:29]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[C:7]([CH2:12][N:13]4[CH2:16][CH:15]([CH:17]5[CH2:18][CH2:19][O:20][CH2:21][CH2:22]5)[CH2:14]4)[N:8]3[CH3:11])=[C:4]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[N:3]=2)[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[N:31]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 1458201H-Benzimidazole-2-methanamineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59605752HCID 59605752, compound

Product 1

HCID 59605806HCID 59605806, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
150 °C

Procedure

A mixture of 2-chloro-9-methyl-6-morpholin-4-yl-8-[3-(tetrahydropyran-4-yl)azetidin-1-ylmethyl]-9H-purine (120 mg, 0.29 mmol), (1H-benzoimidazol-2-yl)methylamine (52 mg, 0.35 mmol), tris(dibenzylideneacetone)dipalladium (14 mg, 0.01 mmol), Xphos (28 mg, 0.06 mmol) and Cs2CO3 (192 mg, 0.59 mmol) in DMF (2.5 mL) was purged with argon then heated at 150° C. for 30 min in a microwave reactor. The reaction mixture was filtered through a pad of celite, washing with EtOAc. The filtrate was concentrated in vacuo and purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-15%) affording 435 as a foam (104 mg, 69%). LCMS (Method I): RT 2.45 min, [M+H]+ 518.4. 1H NMR (CDCl3, 400 MHz): δ 8.48 (d, J=5.0 Hz, 1 H); 8.28 (d, J=8.0 Hz, 1 H); 7.49 (d, J=7.8 Hz, 1 H); 7.19 (m, 1 H); 7.10-7.04 (m, 1 H); 4.34 (m, 4 H); 3.97 (dd, J=11.5, 4.1 Hz, 2 H); 3.90 (t, J=4.7 Hz, 4 H); 3.85 (s, 3 H); 3.82 (s, 2 H); 3.51 (t, J=7.3 Hz, 2 H); 3.42-3.32 (m, 2 H); 3.26 (d, J=5.0 Hz, 3 H); 3.03 (t, J=7.0 Hz, 2 H); 2.34-2.25 (m, 1 H); 1.74-1.62 (m, 1 H); 1.54 (m, 2 H) and 1.27-1.13 (m, 2 H)

Workup

  1. customwas purged with argon
  2. filtrationThe reaction mixture was filtered through a pad of celite
  3. washwashing with EtOAc
  4. concentrationThe filtrate was concentrated in vacuo
  5. custompurified by column chromatography (Si—PCC, MeOH:EtOAc, 0-15%)

Sources & evidence

ORD record
ord-68587b83573a45f482d02cff8634537c
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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