Chlorosuccinimide → (R)-6-(4-Chloro-3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-2-(3,5-dimethyl-1-tosyl-1H-indazol-4-yl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

HRID 80841Notes

Reaction equation

HRID 80841 reaction equation
[CH:1]1([C:4]2[CH:8]=[C:7]([N:9]3[CH2:49][CH2:48][C:12]4[N:13]=[C:14]([C:27]5[C:35]([CH3:36])=[CH:34][CH:33]=[C:32]6[C:28]=5[C:29]([CH3:47])=[N:30][N:31]6[S:37]([C:40]5[CH:46]=[CH:45][C:43]([CH3:44])=[CH:42][CH:41]=5)(=[O:39])=[O:38])[N:15]=[C:16]([N:17]5[CH2:22][CH2:21][C@@H:20]([O:23][CH3:24])[C:19]([CH3:26])([CH3:25])[CH2:18]5)[C:11]=4[CH2:10]3)[N:6]([CH3:50])[N:5]=2)[CH2:3][CH2:2]1.[Cl:51]N1C(=O)CCC1=O>C(Cl)Cl>[Cl:51][C:8]1[C:4]([CH:1]2[CH2:3][CH2:2]2)=[N:5][N:6]([CH3:50])[C:7]=1[N:9]1[CH2:49][CH2:48][C:12]2[N:13]=[C:14]([C:27]3[C:35]([CH3:36])=[CH:34][CH:33]=[C:32]4[C:28]=3[C:29]([CH3:47])=[N:30][N:31]4[S:37]([C:40]3[CH:41]=[CH:42][C:43]([CH3:44])=[CH:45][CH:46]=3)(=[O:39])=[O:38])[N:15]=[C:16]([N:17]3[CH2:22][CH2:21][C@@H:20]([O:23][CH3:24])[C:19]([CH3:25])([CH3:26])[CH2:18]3)[C:11]=2[CH2:10]1

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 71244788HCID 71244788, compound

Product 1

HCID 71244805(R)-6-(4-Chloro-3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-2-(3,5-dimethyl-1-tosyl-1H-indazol-4-yl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-6-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-2-(3,5-dimethyl-1-tosyl-1H-indazol-4-yl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (0.062 g, 0.089 mmol) in DCM (2 mL) under an atmosphere of nitrogen was added N-chlorosuccinimide (0.012 g, 0.089 mmol). The mixture was left to stir for 1 h at rt. The reaction mixture was then directly purified by FCC (40-75% EtOAc/heptanes) to give the title compound. 1H NMR (400 MHz, DICHLOROMETHANE-d2) δ ppm 8.08 (d, J=8.3 Hz, 1 H), 7.79 (d, J=8.3 Hz, 2 H), 7.45 (d, J=8.8 Hz, 1 H), 7.25 (d, J=8.3 Hz, 2 H), 4.32 (d, J=14.7 Hz, 1 H), 4.22 (d, J=14.4 Hz, 1 H), 3.67 (d, J=11.6 Hz, 1 H), 3.58 (s, 3 H), 3.52 (dq, J=12.8, 6.3 Hz, 2 H), 3.28-3.36 (m, 4 H), 3.09 (br. s., 1 H), 2.99 (br. s., 2 H), 2.92 (dd, J=8.6, 3.8 Hz, 1 H), 2.86 (d, J=11.6 Hz, 1 H), 2.72 (s, 2 H), 2.36 (s, 3 H), 2.25 (s, 3 H), 1.88-1.96 (m, 4 H), 1.78-1.88 (m, 1 H), 1.52-1.69 (m, 3 H), 0.94 (s, 3 H), 0.81-0.90 (m, 8 H); MS (ESI+) m/z 729.4 (M+H)+.

Workup

  1. waitThe mixture was left
  2. customThe reaction mixture was then directly purified by FCC (40-75% EtOAc/heptanes)

Sources & evidence

ORD record
ord-f6f955af07f1466d96782093076e1f2c
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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