Hydrochloric Acid → HCID 78324891, compound

HRID 2170169Notes

Reaction equation

HRID 2170169 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([NH:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[C:11]3=[C:22]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH:23]=[CH:24][N:10]3[N:9]=2)[CH:5]=[N:6][CH:7]=1.ClS([N:35]=[C:36]=[O:37])(=O)=O.Cl>C(Cl)Cl>[C:25]1([C:22]2[CH:23]=[CH:24][N:10]3[C:11]=2[C:12]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)=[N:13][C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:36]([NH2:35])=[O:37])[CH:7]=[N:6][CH:5]=2)=[N:9]3)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 70918Chlorosulfonyl isocyanateHCID 90386124HCID 90386124, compound

Product 1

HCID 78324891HCID 78324891, compoundYield 27.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(5-Aminopyridin-3-yl)-5-phenyl-N-(pyridin-2-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (0.100 g, 0.254 mmol) (prepared as in Example 3) was dissolved in CH2Cl2 (10 mL) and chlorosulfonyl isocyanate (0.0330 mL, 0.381 mmol) was added. The reaction mixture was stirred at room temperature for 3 h. Concentrated hydrochloric acid was added until the reaction mixture forms a clear solution. The aqueous mixture was extracted with CH2Cl2 (30 mL) and the organic layer was separated. The aqueous layer was adjusted to pH 11 using saturated solution of sodium hydroxide. The aqueous solution was extracted with CH2Cl2 (20×3 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (Condition B-62 as described in general methods) to obtain 1-(5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridin-3-yl)urea (30.0 mg, 27.0%). LCMS Condition B-14: retention time 1.831 min, [M+1]=437.2. HPLC Condition B-30: retention time 5.48 min, Purity 95.9%. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.91 (d, J=4.8 Hz, 2H), 6.05 (br s, 2H), 6.81 (d, J=2.4 Hz, 1H), 7.27 (t, J=4.8 Hz, 2H), 7.46-7.61 (m, 7H), 7.76 (dt, J=1.6 Hz, J=7.6 Hz, 1H), 7.90 (d, J=2.8 Hz, 1H), 8.38-8.39 (m, 1H), 8.66-8.68 (m, 1H), 8.88 (s, 1H), 8.96 (d, J=1.6 Hz, 1H).

Workup

  1. extractionThe aqueous mixture was extracted with CH2Cl2 (30 mL)
  2. customthe organic layer was separated
  3. extractionThe aqueous solution was extracted with CH2Cl2 (20×3 mL)
  4. dry with materialThe combined organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative HPLC (Condition B-62 as described in general methods)

Sources & evidence

ORD record
ord-e17f0e554afa4785a88ef01c0e08432f
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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