Dimethylformamide → HCID 86681213, compound

HRID 1848240Notes

Reaction equation

HRID 1848240 reaction equation
Br[C:2]1[CH:28]=[C:27]([F:29])[C:5]2[N:6]([CH2:9][C:10]3[CH:26]=[CH:25][C:13]4[N:14]=[C:15]([NH:17][C@@H:18]5[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]5[OH:24])[S:16][C:12]=4[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.[CH3:30][N:31](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].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]>[F:29][C:27]1[C:5]2[N:6]([CH2:9][C:10]3[CH:26]=[CH:25][C:13]4[N:14]=[C:15]([NH:17][C@@H:18]5[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]5[OH:24])[S:16][C:12]=4[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=[C:2]([C:30]#[N:31])[CH:28]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 86681211HCID 86681211, compound

Product 1

HCID 86681213HCID 86681213, compoundYield 2%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst2×HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst2×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×

Conditions

Temperature
100 °C

Procedure

A stirred mixture of (1R,2R)-2-((6-((5-bromo-7-fluoro-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (150 mg, 0.316 mmol) from Example 203, zinc cyanide (111 mg, 0.948 mmol), 1,1′-bis(diphenylphosphino)ferrocene (35 mg, 0.0632 mmol) and anhydrous DMF (2 mL) was purged with a stream of argon. To the mixture was added palladium(trisdibenzylideneacetone) (0) (29 mg, 0.0316 mmol) and the mixture was heated in a sealed tube 100° C. for 6 h. The mixture was cooled and additional zinc cyanide (111 mg, 0.948 mmol), 1,1′-bis(diphenylphosphino)ferrocene (35 mg, 0.0632 mmol), and palladium(trisdibenzylideneacetone) (0) (29 mg, 0.0316 mmol) were added, and heating in a sealed tube was continued at 100° C. for 15 h. The mixture was cooled to rt and purified directly by reverse-phase preparative HPLC using a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase to afford (7-fluoro-1-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile (2.6 mg, 2%) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 8.70 (s, 1H), 8.13 (s, 1H), 8.02 (d, J=7.6 Hz, 1H), 7.63 (d, J=11.1 Hz, 1H), 7.57 (s, 1H), 7.29 (d, J=8.1 Hz, 1H), 7.10 (d, J=8.1 Hz, 1H), 5.58 (s, 2H), 4.77 (br s, 1H), 3.50 (br m, 1H), 3.30 (br m, 1H), 2.02 (m, 1H), 1.87 (m, 1H), 1.55-1.67 (m, 2H), 1.12-1.32 (m, 4H); LCMS (ESI) m/z 422 (M+H)+.

Workup

  1. customwas purged with a stream of argon
  2. temperatureThe mixture was cooled
  3. temperatureheating in a sealed tube
  4. temperatureThe mixture was cooled to rt
  5. custompurified directly by reverse-phase preparative HPLC
  6. additiona mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase

Sources & evidence

ORD record
ord-b6b69dcdc54049219a8982656c6beca7
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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