tert-butyl 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydropyridine-1(2H)-carboxylate → HCID 178434298, compound

HRID 2375922Notes

Reaction equation

HRID 2375922 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[NH:23][C:17]3[N:18]=[CH:19][N:20]=[C:21](Cl)[C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][C:25]1[C:33]2[C:28](=[CH:29][CH:30]=[C:31]([NH2:34])[CH:32]=2)[NH:27][N:26]=1>CC(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[NH:23][C:17]3[N:18]=[CH:19][N:20]=[C:21]([NH:34][C:31]4[CH:32]=[C:33]5[C:28](=[CH:29][CH:30]=4)[NH:27][N:26]=[C:25]5[CH3:24])[C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 58709797tert-butyl 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydropyridine-1(2H)-carboxylateHCID 178434299HCID 178434299, compound

Product 1

HCID 178434298HCID 178434298, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (50.1 mg, 0.150 mmol) and 3-methyl-1H-indazol-5-ylamine (25.0 mg, 0.170 mmol) in iPrOH (2.5 mL) in a sealed tube was heated to 90° C. (bath temp.) for 16 h. The solvent was evaporated, water/NaHCO3 solution was added, the mixture was extracted with CH2Cl2 (3×30 mL), and the combined extracts were washed with brine and dried over MgSO4. The extracts were filtered through a pad of silica gel, washing with 5% MeOH in CH2Cl2 until no more product eluted as indicated by TLC. Concentration in vacuo gave a light brown solid. The solid was triturated with MeOH, filtered, washed with more MeOH, and dried in vacuo overnight. One obtained the title compound as white solid, mp. 245-250° C. (decomp.). 1H NMR (DMSO-d6, 400 MHz): δ=1.43 (s, 9H), 2.42-2.50 (brs, 2H), 2.47 (s, 3H), 3.53-3.59 (me, 2H), 3.99-4.08 (m, 2H), 6.38 (brs, 1H), 6.73 (brs, 1H), 7.43 (d, J=8.8 Hz, 1H), 7.69 (dd, J=1.6, 8.8 Hz, 1H), 8.15 (s, 1H), 8.23 (s, 1H), 9.32 (s, 1H), 11.88 (brs, 1H), 12.54 (s, 1H). MS (ES+): m/z 446.0 (100) [MH+]. HPLC: tR=2.4 min (ZQ2000, polar—5 min).

Workup

  1. customThe solvent was evaporated
  2. additionwater/NaHCO3 solution was added
  3. extractionthe mixture was extracted with CH2Cl2 (3×30 mL)
  4. washthe combined extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationThe extracts were filtered through a pad of silica gel
  7. washwashing with 5% MeOH in CH2Cl2 until no more product
  8. washeluted
  9. concentrationConcentration in vacuo
  10. customgave a light brown solid
  11. customThe solid was triturated with MeOH
  12. filtrationfiltered
  13. washwashed with more MeOH
  14. customdried in vacuo overnight

Sources & evidence

ORD record
ord-964c868c3f884f028aeca5b3d42bd14b
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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