4-(N-Boc-amino)piperidine → tert-butyl (1-(4-(5-(dimethylcarbamoyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrimidin-2-yl)piperidin-4-yl)carbamate

HRID 1529445Notes

Reaction equation

HRID 1529445 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]([N:19]([CH3:21])[CH3:20])=[O:18])[CH:15]=3)[N:10]([CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)[N:9]=2)[CH:5]=[CH:4][N:3]=1.[NH:28]1[CH2:33][CH2:32][CH:31]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:30][CH2:29]1>CS(C)=O>[CH3:20][N:19]([CH3:21])[C:17]([C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][O:23]1)[N:9]=[C:8]2[C:6]1[CH:5]=[CH:4][N:3]=[C:2]([N:28]2[CH2:29][CH2:30][CH:31]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:39])([CH3:38])[CH3:40])[CH2:32][CH2:33]2)[N:7]=1)=[O:18]

Participants

4

Reactant 2

HCID 7238334-(N-Boc-amino)piperidineHCID 867097953-(2-chloropyrimidin-4-yl)-N,N-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxamide

Product 1

HCID 86709796tert-butyl (1-(4-(5-(dimethylcarbamoyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrimidin-2-yl)piperidin-4-yl)carbamateYield 56.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-(2-chloropyrimidin-4-yl)-N,N-dimethyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxamide (0.5 g, 1.29 mmol) in DMSO (5 mL) was added tert-butyl piperidin-4-ylcarbamate (0.311 g, 1.54 mmol) and the reaction was stirred for 12 h at 100° C. The reaction was quenched with ice cold water (5 mL) to give the off white precipitate. The suspension was filtered, washed with ice cold water and dried to give tert-butyl (1-(4-(5-(dimethylcarbamoyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrimidin-2-yl)piperidin-4-yl)carbamate (0.4 g, 48%) as a off white solid. MS (ESI, pos. ion) m/z: 550.3 (M+1); 1H NMR (400 MHz, DMSO-d6) δ 8.54 (s, 1H), 8.45 (d, 1 H, J=5.1 Hz), 7.90 (d, 1 H, J=8.8 Hz), 7.35-7.65 (m, 1H), 7.28 (d, 1 H, J=5.1 Hz), 6.89 (d, 1 H, J=7.7 Hz), 6.01 (dd, 1 H, J=7.4, 2.0 Hz), 4.64 (d, 2 H, J=12.9 Hz), 3.90-4.04 (m, 1H), 3.76-3.82 (m, 1H), 3.60 (s, 1H), 3.16 (t, 2 H, J=11.8 Hz), 3.02 (s, 6H), 2.03-2.06 (m, 2H), 1.82-1.86 (m, 3H), 1.62 (bs, 2H), 1.23 (m, 12H).

Workup

  1. customThe reaction was quenched with ice cold water (5 mL)
  2. customto give the off white precipitate
  3. filtrationThe suspension was filtered
  4. washwashed with ice cold water
  5. customdried

Sources & evidence

ORD record
ord-907b121eafba4176b7911be161c99c9c
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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