Methanesulfonyl chloride → HCID 86707710, compound

HRID 1408962Notes

Reaction equation

HRID 1408962 reaction equation
[NH2:1][C@@:2]1([CH3:30])[CH2:6][CH2:5][C@@H:4]([NH:7][C:8]2[C:9]3[N:10]([CH:17]=[C:18]([C:20]4[CH:21]=[N:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=4)[CH:19]=3)[N:11]=[CH:12][C:13]=2[C:14]([NH2:16])=[O:15])[C:3]1([CH3:29])[CH3:28].C(N(CC)C(C)C)(C)C.[CH3:40][S:41](Cl)(=[O:43])=[O:42]>CN(C1C=CN=CC=1)C.ClCCl>[CH3:27][O:26][C:23]1[N:22]=[CH:21][C:20]([C:18]2[CH:19]=[C:9]3[C:8]([NH:7][C@@H:4]4[CH2:5][CH2:6][C@:2]([CH3:30])([NH:1][S:41]([CH3:40])(=[O:43])=[O:42])[C:3]4([CH3:29])[CH3:28])=[C:13]([C:14]([NH2:16])=[O:15])[CH:12]=[N:11][N:10]3[CH:17]=2)=[CH:25][CH:24]=1

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 86707711HCID 86707711, compound

Product 1

HCID 86707710HCID 86707710, compoundYield 37.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

4-(N,N-dimethylamino)pyridine (15.7 mg, 0.129 mmol) was added to a solution of 4-((1R,3S)-3-amino-2,2,3-trimethylcyclopentylamino)-6-(6-methoxypyridin-3-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide (97.5 mg, 0.138 mmol, from Example 232), N,N-diisopropylethylamine (0.080 mL, 0.458 mmol) and methanesulfonyl chloride (0.030 mL, 0.385 mmol) in dichloromethane (1 mL). After 1 h at room temperature, the mixture was purified by silica gel chromatography, eluting with 0-10% methanol in dichloromethane. The fractions containing the desired product were concentrated. The material was further purified with reverse phase HPLC (Waters Xbridge 19×100 mm), eluting with 20-80% solvent B (10% methanol-90% water-0.1% TFA) in solvent A (90% methanol-10% water-0.1% TFA), to give 6-(6-methoxy-3-pyridinyl)-4-(((1R,3S)-2,2,3-trimethyl-3-((methylsulfonyl)amino)-cyclopentyl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide as white solid (25.1 mg, 37% yield). 1H NMR (400 MHz, methanol-d4) δ ppm 8.47 (1 H, d, J=1.98 Hz), 8.15 (1 H, s), 8.07 (1 H, dd, J=8.58, 2.42 Hz), 7.95 (1 H, d, J=1.76 Hz), 7.15 (1 H, d, J=1.54 Hz), 6.94 (1 H, d, J=8.58 Hz), 4.58 (1 H, t, J=8.25 Hz), 3.98 (3 H, s), 3.06 (3 H, s), 2.42-2.53 (2 H, m), 1.93-2.05 (1 H, m), 1.73-1.84 (1 H, m), 1.53 (3 H, s), 1.16 (3 H, s), 1.04 (3 H, s); MS (ES+) m/z: 487.3 (M+H); LC retention time: 3.843 min (analytical HPLC Method F).

Workup

  1. customthe mixture was purified by silica gel chromatography
  2. washeluting with 0-10% methanol in dichloromethane
  3. additionThe fractions containing the desired product
  4. concentrationwere concentrated
  5. customThe material was further purified with reverse phase HPLC (Waters Xbridge 19×100 mm)
  6. washeluting with 20-80% solvent B (10% methanol-90% water-0.1% TFA) in solvent A (90% methanol-10% water-0.1% TFA)

Sources & evidence

ORD record
ord-99582a2c42614c9c952c466f5faa997b
Source dataset
uspto-grants-2014_12
Patent number
US08921368B2

Reaction notes

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