Acetic Acid → HCID 118022924, compound

HRID 1498848Notes

Reaction equation

HRID 1498848 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]3[N:14]([CH:15]=2)[N:13]=[CH:12][N:11]=[C:10]3[N:16]2[CH2:21][CH2:20][N:19]([C:22]3[N:27]=[CH:26][C:25]([C@H:28]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)N)=[CH:24][N:23]=3)[CH2:18][CH2:17]2)[CH:4]=[N:3]1.C=O.[C:38]([BH3-])#[N:39].[Na+].[C:42](O)(=O)C.C([O-])(O)=O.[Na+]>CC#N>[CH3:42][N:39]([CH3:38])[C@H:28]([C:25]1[CH:24]=[N:23][C:22]([N:19]2[CH2:20][CH2:21][N:16]([C:10]3[C:9]4=[CH:8][C:7]([C:5]5[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=5)=[CH:15][N:14]4[N:13]=[CH:12][N:11]=3)[CH2:17][CH2:18]2)=[N:27][CH:26]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 118022772HCID 118022772, compound

Product 1

HCID 118022924HCID 118022924, compoundYield 19.65%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(S)-(2-(4-(6-(1-Methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl)piperazin-1-yl)pyrimidin-5-yl)(phenyl)methanamine (72 mg, 0.154 mmol) and formaldehyde (125 mg, 1.543 mmol) were taken up in MeCN (1.5 mL). Sodium cyanoborohydride (25 mg, 0.398 mmol) was added, followed by acetic acid (0.02 mL, 0.349 mmol) and the resulting mixture was stirred at room temperature for 3 hours. Saturated NaHCO3 was added and the products extracted into DCM (×2). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification of the residue by MPLC (0-10% MeOH-DCM), followed by MPLC (0-10% MeOH-EtOAc), followed by MPLC (0-8% MeOH-EtOAc) gave (S)—N,N-dimethyl-1-(2-(4-(6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl)piperazin-1-yl)pyrimidin-5-yl)-1-phenylmethanamine (15 mg, 0.030 mmol, 19.65% yield).

Workup

  1. extractionthe products extracted into DCM (×2)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by MPLC (0-10% MeOH-DCM)

Sources & evidence

ORD record
ord-2458b99fee024bc89b4d80969028e000
Source dataset
uspto-grants-2015_12
Patent number
US09200002B2

Reaction notes

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