Water → HCID 86677348, compound

HRID 1842823Notes

Reaction equation

HRID 1842823 reaction equation
[CH3:1][O:2][C:3]1[C:4]([NH:25][C:26]2[N:31]=[C:30]([C:32]3[C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[N:34]([CH3:41])[CH:33]=3)[CH:29]=[CH:28][N:27]=2)=[CH:5][C:6]([N+:22]([O-])=O)=[C:7]([N:9]([CH3:21])[CH2:10][CH2:11][N:12]([CH3:20])[C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH:8]=1.[NH4+].[Cl-].O>C(O)C.[Fe]>[NH2:22][C:6]1[CH:5]=[C:4]([NH:25][C:26]2[N:31]=[C:30]([C:32]3[C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[N:34]([CH3:41])[CH:33]=3)[CH:29]=[CH:28][N:27]=2)[C:3]([O:2][CH3:1])=[CH:8][C:7]=1[N:9]([CH3:21])[CH2:10][CH2:11][N:12]([CH3:20])[C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 71269957HCID 71269957, compound2×

Product 1

HCID 86677348HCID 86677348, compoundYield 94%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

tert-Butyl N-[2-[[5-methoxy-4-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]-2-nitrophenyl]-methylamino]ethyl]-N-methylcarbamate (Intermediate 172, 428 mg, 0.76 mmol), iron (255 mg, 4.57 mmol) and NH4Cl (30.6 mg, 0.57 mmol) were heated in ethanol (16 mL) and water (5.33 mL) at reflux for 1.5 h (heating block at 100° C.) and then the mixture was cooled and concentrated in vacuo. The resulting residue was triturated in 10% CH3OH/CH2Cl2 (30 mL) and filtered. The residues were triturated again with 10% CH3OH/CH2Cl2 (30 mL) and filtered. The combined filtrates were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 0-5% CH3OH in CH2Cl2 gave the title compound (380 mg, 94%) as a light brown foam; 1H NMR: 1.41 (9H, s), 2.64 (3H, s), 2.80 (3H, s), 2.95 (2H, t), 3.34 (2H, t), 3.77 (3H, s), 3.89 (3H, s), 4.40 (2H, s), 6.78 (1H, s), 7.14-7.20 (2H, m), 7.23-7.27 (1H, m), 7.52 (1H, d), 7.55 (1H, s), 7.75 (1H, s), 8.28 (1H, d), 8.29 (1H, s), 8.42 (1H, d); m/z: ES+ MH+ 532.37.

Workup

  1. temperaturethe mixture was cooled
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was triturated in 10% CH3OH/CH2Cl2 (30 mL)
  4. filtrationfiltered
  5. customThe residues were triturated again with 10% CH3OH/CH2Cl2 (30 mL)
  6. filtrationfiltered
  7. washThe combined filtrates were washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customPurification by FCC
  11. washeluting with 0-5% CH3OH in CH2Cl2

Sources & evidence

ORD record
ord-f9cbbb4693924408943cc02a4581f9f7
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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