Dichloromethane → (R)-(6-((6-chloropyridin-3-yl)sulfonyl)-1-(4-fluorophenyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(pyridin-2-yl)methanone

HRID 920617Notes

Reaction equation

HRID 920617 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[C:14]4[C@:19]([C:21]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=5)=[O:22])([CH2:20][C:11]=3[CH:10]=[N:9]2)[CH2:18][NH:17][CH2:16][CH2:15]4)=[CH:4][CH:3]=1.ClCCl.C(NC(C)C)(C)C.[Cl:39][C:40]1[N:45]=[CH:44][C:43]([S:46](Cl)(=[O:48])=[O:47])=[CH:42][CH:41]=1.C(N(C(C)C)CC)(C)C>>[Cl:39][C:40]1[N:45]=[CH:44][C:43]([S:46]([N:17]2[CH2:16][CH2:15][C:14]3[C@:19]([C:21]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)=[O:22])([CH2:20][C:11]4[CH:10]=[N:9][N:8]([C:5]5[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=5)[C:12]=4[CH:13]=3)[CH2:18]2)(=[O:48])=[O:47])=[CH:42][CH:41]=1

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 7912DiisopropylamineHCID 81531DiisopropylethylamineHCID 27927922-Chloro-5-pyridinesulfonyl chlorideHCID 86709980(R)-(1-(4-fluorophenyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(pyridin-2-yl)methanone

Product 1

HCID 73053203(R)-(6-((6-chloropyridin-3-yl)sulfonyl)-1-(4-fluorophenyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(pyridin-2-yl)methanone

Procedure

A solution of (R)-(1-(4-fluorophenyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(pyridin-2-yl)methanone in dichloromethane (2.5 mL) (2.7 mL, ˜0.2 mmol) containing diisopropylamine (174 μL, 1 mmol) was added to 6-chloro-pyridine-3-sulfonyl chloride (53 mg, 0.25 mmol) and diisopropylethylamine (100 μL, 0.57 mmol) and the mixture stirred for 16 hours. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (gradient: 20-30% ethyl acetate in cyclohexane) to afford (R)-(6-((6-chloropyridin-3-yl)sulfonyl)-1-(4-fluorophenyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(pyridin-2-yl)methanone as a white solid (85 mg). LCMS (Method B ESI): RT 3.92 min, m+H=550.0; 1H NMR (400 MHz, CDCl3): δ 8.66 (d, J=2.5 Hz, 1 H); 8.61 (d, J=4.7 Hz, 1 H); 7.85-7.86 (m, 3 H); 7.48-7.49 (m, 1 H); 7.42-7.43 (m, 2 H); 7.35 (d, J=8.4 Hz, 1 H); 7.27 (s, 1 H); 7.15-7.16 (m, 2 H); 6.50 (s, 1 H); 5.57 (d, J=12.4 Hz, 1 H); 4.23 (d, J=16.9 Hz, 1 H); 3.85-3.95 (m, 1H); 2.86-2.87 (m, 3 H); 2.66 (d, J=11.9 Hz, 1 H); 2.53 (d, J=15.1 Hz, 1 H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was purified by column chromatography on silica gel (gradient: 20-30% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-9f50761e18aa49599be3b9b8a69d3595
Source dataset
uspto-grants-2016_03
Patent number
US09273047B2

Reaction notes

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