1-Methylpiperazine → HCID 58346467, compound

HRID 222022Notes

Reaction equation

HRID 222022 reaction equation
CS(O[CH2:6][CH2:7][N:8]1[CH:16]=[C:15]2[C:10]([CH2:11][CH2:12][C:13]3[C:19]4[C:20]([NH:24][C:25]5[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]6[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=6)=[C:27]([Cl:40])[CH:26]=5)=[N:21][CH:22]=[N:23][C:18]=4[S:17][C:14]=32)=[N:9]1)(=O)=O.[CH3:41][N:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1.C(N(C(C)C)CC)(C)C>CC#N>[Cl:40][C:27]1[CH:26]=[C:25]([NH:24][C:20]2[N:21]=[CH:22][N:23]=[C:18]3[S:17][C:14]4[C:15]5[C:10]([CH2:11][CH2:12][C:13]=4[C:19]=23)=[N:9][N:8]([CH2:7][CH2:6][N:45]2[CH2:46][CH2:47][N:42]([CH3:41])[CH2:43][CH2:44]2)[CH:16]=5)[CH:30]=[CH:29][C:28]=1[O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=1

Participants

5

Reactant 3

HCID 531671-MethylpiperazineHCID 81531DiisopropylethylamineHCID 58346443HCID 58346443, compound

Product 1

HCID 58346467HCID 58346467, compoundYield 55.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To 250 mL CH3CN were sequentially added 2-[6-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-4,5-dihydro-2H-pyrimido[5′,4′:4,5]thieno[2,3-e]indazol-2-yl]ethyl methanesulfonate (5.80 g, 9.67 mmol), 1-methylpiperazine (3.22 mL, 29.0 mmol), and diisopropylethylamine (3.37 mL, 19.3 mmol). The opaque white suspension was stirred with heating to reflux, upon which the contents turn brown and homogeneous. After 15 h the mixture was removed from heating, and allowed to cool to rt. The contents were concentrated under reduced pressure to 10% volume, diluted with CH2Cl2 (150 mL), and washed with aq NH4Cl (50 mL). The aqueous layer was separated and extracted with CH2Cl2 (50 mL), and the combined organic layers then washed with sat. NaHCO3 (2×100 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The solid product was triturated from methanol and then recrystallized from ethanol to afford the final product (3.22 g, 55%) as an off-white solid. 1H-NMR (CD2Cl2) δ 1.98 (s, 3H), 2.30-2.50 (broad m, 8H), 2.68 (t, 2H), 2.98 (t, 2H), 3.25 (t, 2H), 4.08 (t, 2H), 5.07 (s, 2H), 6.93-7.00 (m, 3H), 7.14-7.20 (m, 2H), 7.25-7.39 (m, 2H), 7.75 (s, 1H), 8.31 (s, 1H); LCMS RT=3.15 min; [M+H]+=604.3.

Workup

  1. temperaturewith heating
  2. temperatureto reflux, upon which the contents
  3. customAfter 15 h the mixture was removed
  4. temperaturefrom heating
  5. concentrationThe contents were concentrated under reduced pressure to 10% volume
  6. additiondiluted with CH2Cl2 (150 mL)
  7. washwashed with aq NH4Cl (50 mL)
  8. customThe aqueous layer was separated
  9. extractionextracted with CH2Cl2 (50 mL)
  10. washthe combined organic layers then washed with sat. NaHCO3 (2×100 mL)
  11. dry with materialThe organic layer was dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe solid product was triturated from methanol
  15. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-90745bdb89544db0a65115ee79fa2277
Source dataset
uspto-grants-2012_06
Patent number
US08207172B2

Reaction notes

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