Chlorosulfonyl isocyanate → 1-(5-(4-(Benzylamino)-5-phenylphthalazin-1-yl)pyridin-3-yl)urea

HRID 593713Notes

Reaction equation

HRID 593713 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[C:13]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH:14]=[CH:15][CH:16]=3)[C:11]([NH:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[N:10][N:9]=2)[CH:5]=[N:6][CH:7]=1.ClS([N:36]=[C:37]=[O:38])(=O)=O>ClCCl>[CH2:25]([NH:24][C:11]1[C:12]2[C:17](=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:37]([NH2:36])=[O:38])[CH:7]=[N:6][CH:5]=2)=[N:9][N:10]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

4

Reactant 2

HCID 70918Chlorosulfonyl isocyanateHCID 904354934-(5-Aminopyridin-3-yl)-N-benzyl-8-phenylphthalazin-1-amine

Product 1

HCID 862704851-(5-(4-(Benzylamino)-5-phenylphthalazin-1-yl)pyridin-3-yl)ureaYield 3.01%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(5-aminopyridin-3-yl)-N-benzyl-8-phenylphthalazin-1-amine (60.0 mg, 0.149 mmol) in dichloromethane (10 mL) was added chlorosulfonyl isocyanate (0.0191 mL, 0.223 mmol) dropwise at 0° C. and the reaction mixture allowed to stir for 2 h while warming to ambient temperature. The volatile components were evaporated under reduced pressure and the resulting residue was cooled to 0° C. 1.5N HCl was added and the reaction mixture stirred for an additional 2 h. The reaction mixture was adjusted to pH˜8 by the addition of aqueous sodium bicarbonate. The resulting solution was extracted with ethyl acetate (3×5 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by preparative HPLC (Condition 30 as described in general methods) to afford 1-(5-(4-(benzylamino)-5-phenylphthalazin-1-yl)pyridin-3-yl)urea (2.00 mg, 3.01%) as a white solid. LCMS (Condition 4): retention time 2.32 min, [M+1]=447.2. HPLC (Condition 28): retention time=6.13 min, purity 98.80%. 1H NMR (400 MHz, DMSO-d6) δ 4.51 (d, J=4.8 Hz, 2 H), 5.04 (t, J=4.8 Hz, 1 H), 6.10 (s, 2 H), 7.02 (dd, J=1.2 Hz, J=6.8 Hz, 2 H), 7.22-7.28 (m, 3 H), 7.43-7.51 (m, 5 H), 7.68 (dd, J=1.2 Hz, J=7.6 Hz, 1 H), 7.85-7.92 (m, 2 H), 8.24 (dd, J=2.0 Hz, J=2.4 Hz, 1 H), 8.37 (d, J=2.0 Hz, 1 H), 8.64 (d, J=2.4 Hz, 1 H), 8.94 (s, 1 H).

Workup

  1. customThe volatile components were evaporated under reduced pressure
  2. temperaturethe resulting residue was cooled to 0° C
  3. addition1.5N HCl was added
  4. stirringthe reaction mixture stirred for an additional 2 h
  5. additionThe reaction mixture was adjusted to pH˜8 by the addition of aqueous sodium bicarbonate
  6. extractionThe resulting solution was extracted with ethyl acetate (3×5 mL)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue was purified by preparative HPLC (Condition 30 as described in general methods)

Sources & evidence

ORD record
ord-68ddf134d5234ec99eb5100a298ae39f
Source dataset
uspto-grants-2016_01
Patent number
US09242966B2

Reaction notes

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