Pyridine → 1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-6-[(phenylsulfonyl)amino]-1H-indazole-4-carboxamide

HRID 1476437Notes

Reaction equation

HRID 1476437 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]2[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=2[CH3:26])=[O:17])[C:5]2[CH:6]=[N:7][N:8]([CH:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)[C:9]=2[CH:10]=1.N1C=CC=CC=1.[C:35]1([S:41](Cl)(=[O:43])=[O:42])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C(Cl)Cl>[CH:11]1([N:8]2[C:9]3[CH:10]=[C:2]([NH:1][S:41]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)(=[O:43])=[O:42])[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]4[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=4[CH3:26])=[O:17])[C:5]=3[CH:6]=[N:7]2)[CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 7369Benzenesulfonyl chlorideHCID 545973016-amino-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide

Product 1

HCID 545973021-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-6-[(phenylsulfonyl)amino]-1H-indazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

6-amino-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (30 mg, 0.079 mmol) was suspended in DCM (3 mL) followed by pyridine (0.032 mL, 0.395 mmol). The contents were vigorously stirred and then benzenesulfonyl chloride (0.011 mL, 0.087 mmol) was added and the contents stirred at RT for 1 h. The volatiles were removed in vacuo and dried on hi-vac for 1 h. The crude product was purified by reverse phase HPLC (Gradient B: 15-70%. A: Water+0.1% TFA. B: CH3CN+0.1% TFA). The product was neutralized with water and sat. NaHCO3, and extracted with 10% THF/EtOAC (hot) in duplicate. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The solid was concentrated from DCM and dried in vacuum oven for 4 h at 45° C. The title compound was collected as 30 mg (72%); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.68 (td, J=5.49, 3.41 Hz, 2H), 1.75-1.94 (m, 4H), 1.99-2.10 (m, 2H), 2.12 (s, 3H), 2.20 (s, 3H), 4.30 (d, J=5.05 Hz, 2H), 4.89-5.04 (m, 1H), 5.89 (s, 1H), 7.22 (d, J=1.52 Hz, 1H), 7.36 (s, 1H), 7.48-7.63 (m, 3H), 7.77-7.84 (m, 2H), 8.11 (s, 1H), 8.36 (t, J=5.05 Hz, 1H), 10.56 (s, 1H), 11.55 (s, 1H); LC-MS (ES) m/z=519.2 [M+H]

Workup

  1. stirringthe contents stirred at RT for 1 h
  2. customThe volatiles were removed in vacuo
  3. customdried on hi-vac for 1 h
  4. customThe crude product was purified by reverse phase HPLC (Gradient B
  5. extractionextracted with 10% THF/EtOAC (hot) in duplicate
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. concentrationThe solid was concentrated from DCM
  10. customdried in vacuum oven for 4 h at 45° C
  11. customThe title compound was collected as 30 mg (72%)

Sources & evidence

ORD record
ord-0dec542d77174ffe8a82c09f05255d6c
Source dataset
uspto-grants-2015_04
Patent number
US09018382B2

Reaction notes

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