Acetic Acid → HCID 178505709, compound

HRID 1623292Notes

Reaction equation

HRID 1623292 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][CH:29]=1)[CH2:5][NH:6][C:7]1[N:12]=[C:11]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C@H:20]3[CH2:25][CH2:24][C@H:23]([NH2:26])[CH2:22][CH2:21]3)[CH:14]=2)[CH:10]=[N:9][CH:8]=1.C(O)(=O)C.[CH:34](=O)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CS(C)=O.CN1C(=O)CCC1>[CH2:34]([NH:26][C@H:23]1[CH2:22][CH2:21][C@H:20]([NH:19][C:15]2[CH:14]=[C:13]([C:11]3[CH:10]=[N:9][CH:8]=[C:7]([NH:6][CH2:5][C:4]4[CH:27]=[CH:28][CH:29]=[C:2]([F:1])[CH:3]=4)[N:12]=3)[CH:18]=[CH:17][N:16]=2)[CH2:25][CH2:24]1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 240BenzaldehydeHCID 5049666Sodium triacetoxyborohydride2×HCID 178511596HCID 178511596, compound

Product 1

HCID 178505709HCID 178505709, compoundYield 30.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To trans-N1-(4-(6-(3-fluorobenzylamino)pyrazin-2-yl)pyridin-2-yl)cyclohexane-1,4-diamine (19 mg, 0.048 mmol) was added NMP (0.6 ml), acetic acid (0.042 ml, 0.726 mmol) and benzaldehyde (10.27 mg, 0.097 mmol). The resulting reaction mixture was stirred overnight at ambient temperature. To the stirred reaction mixture was added sodium triacetoxyborohydride (41.0 mg, 0.194 mmol) and the resulting mixture was stirred overnight (24 hours) at ambient temperature. To the reaction mixture then was added additional sodium triacetoxyborohydride (21.0 mg, 0.099 mmol) and the resulting mixture was stirred for an additional 2 more hours. To the crude mixture then was added 0.8 ml of DMSO, filtered and purified by prep LC. After lyphilization, 7.0 mg of the title compound was obtained as a TFA salt. LCMS (m/z): 483.2 (MH+), retention time=0.65 min.; 1H NMR (300 MHz, METHANOL-d4, 25° C.) δ ppm 1.35-1.51 (m, 2H) 1.51-1.69 (m, 2H) 2.04-2.36 (m, 4H) 3.08-3.18 (m, 1H) 3.56-3.70 (m, 1H) 4.16 (s, 2H) 4.60 (s, 2H) 6.82-6.93 (m, 1H) 7.03 (d, J=9.67 Hz, 1H) 7.11 (d, J=7.62 Hz, 1H) 7.19-7.29 (m, 1H) 7.32 (d, J=6.74 Hz, 1H) 7.35-7.46 (m, 5H) 7.54 (s, 1H) 7.80 (d, J=6.74 Hz, 1H) 7.97 (s, 1H) 8.25 (s, 1H)

Workup

  1. customThe resulting reaction mixture
  2. customTo the stirred reaction mixture
  3. stirringthe resulting mixture was stirred overnight (24 hours) at ambient temperature
  4. stirringthe resulting mixture was stirred for an additional 2 more hours
  5. filtrationfiltered
  6. custompurified by prep LC

Sources & evidence

ORD record
ord-1dd9cb8e1b334d05b797b7d03072e391
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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