Water → (S)-benzyl 3-(ethyl(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidine-1-carboxylate

HRID 919581Notes

Reaction equation

HRID 919581 reaction equation
[CH2:1]([NH:3][C@H:4]1[CH2:9][CH2:8][CH2:7][N:6]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:5]1)[CH3:2].Cl[C:21]1[C:22]2[CH:29]=[CH:28][N:27]([S:30]([C:33]3[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=3)(=[O:32])=[O:31])[C:23]=2[N:24]=[CH:25][N:26]=1.CCN(C(C)C)C(C)C.O>CN(C=O)C>[CH2:1]([N:3]([C:21]1[C:22]2[CH:29]=[CH:28][N:27]([S:30]([C:33]3[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=3)(=[O:31])=[O:32])[C:23]=2[N:24]=[CH:25][N:26]=1)[C@H:4]1[CH2:9][CH2:8][CH2:7][N:6]([C:10]([O:12][CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[O:11])[CH2:5]1)[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 442289674-Chloro-7-(p-toluenesulfonyl)-7H-pyrrolo[2,3-d]pyrimidineHCID 66569232(S)-benzyl 3-(ethylamino)piperidine-1-carboxylate

Product 1

HCID 86706456(S)-benzyl 3-(ethyl(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidine-1-carboxylateYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-benzyl 3-(ethylamino)piperidine-1-carboxylate (200 mg, 0.76 mmol), 4-chloro-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine (234 mg, 0.76 mmol) and DIEA (0.27 mL, 1.52 mmol) in DMF (3 mL) was heated to 100° C. for 4 h. The reaction was cooled to rt, diluted with ice cooled water (10 mL) and extracted with EtOAc (3×25 mL). The combined EtOAc layer was dried over Na2SO4 and concentrated in vacuo to give the crude product that was purified by column chromatography (silica gel, gradient 0-10% EtOAc hexane) to afford the titled intermediate (300 mg, 73%). 1H NMR (400 MHz, DMSO-d6): δ 8.22 (d, J=5.6 Hz, 1H), 7.98 (d, J=8.0 Hz, 2H), 7.95 (s, 1H), 7.58-7.57 (m, 1H), 7.43 (d, J=8.0 Hz, 2H), 7.39-7.29 (m, 5H), 5.12 and 5.09 (2s, 2H), 4.69-4.63 (m, 1H), 4.05-3.98 (m, 3H), 3.65-3.63 (m, 2H), 3.01-2.77 (m, 1H), 2.36 (s, 3H), 1.89-1.75 (m, 3H), 1.51-1.39 (m, 1H), 1.17 (t, J=6.8 Hz, 3H). LC-MS: m/z [M+1]=534.

Workup

  1. additiondiluted with ice
  2. extractionextracted with EtOAc (3×25 mL)
  3. dry with materialThe combined EtOAc layer was dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customto give the crude product that
  6. customwas purified by column chromatography (silica gel, gradient 0-10% EtOAc hexane)

Sources & evidence

ORD record
ord-b4474a0a65fa42ed80cbc731cf540e46
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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