Hexane → HCID 59380506, compound

HRID 2353845Notes

Reaction equation

HRID 2353845 reaction equation
C[Al](C)C.CCCCCC.[CH2:11]([N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)[CH3:12].[Cl:19][C:20]1[CH:21]=[C:22]([NH:35][C:36]2[C:37]3[C:44]4[CH:45]=[CH:46][C:47](/[CH:49]=[CH:50]/[C:51]([O:53]C)=O)=[CH:48][C:43]=4[S:42][C:38]=3[N:39]=[CH:40][N:41]=2)[CH:23]=[CH:24][C:25]=1[O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=1.[NH4+].[Cl-]>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:19][C:20]1[CH:21]=[C:22]([NH:35][C:36]2[C:37]3[C:44]4[CH:45]=[CH:46][C:47](/[CH:49]=[CH:50]/[C:51]([N:16]5[CH2:17][CH2:18][N:13]([CH2:11][CH3:12])[CH2:14][CH2:15]5)=[O:53])=[CH:48][C:43]=4[S:42][C:38]=3[N:39]=[CH:40][N:41]=2)[CH:23]=[CH:24][C:25]=1[O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=1

Participants

8

Reactant 5

HCID 8058HexaneHCID 25517Ammonium ChlorideHCID 791961-EthylpiperazineHCID 16682925TrimethylaluminumHCID 59380391HCID 59380391, compound

Product 1

HCID 59380506HCID 59380506, compoundYield 86.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred and cold (0° C.) solution of toluene (5 mL) was added trimethyl aluminum in hexane (2M, 0.77 mL, 1.54 mmol, 4 equiv) and stirred for 10 min at 0° C. followed by addition of 1-ethyl piperazine (48 mg, 0.42 mmol, 1.1 equiv). The resulting mixture was stirred for an additional 5 min at 0° C. and then warmed to rt. A suspension of methyl (2E)-3-[4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)[1]benzothieno[2,3-d]pyrimidin-7-yl]acrylate (200 mg) in toluene was added to the above generated mixture. The resulting mixture were heated at 100° C. for 16 h. after cooled to rt, it poured into a cold mixture (0° C.) of NH4Cl aq solution and EtOAc. The resulting gel-like mixture was filtered through a pad of Celite® and pad was washed with EtOAc. The combined EtOAc layers were dried over MgSO4 and concentrated in vacuo. The residue was carefully triturated with ether to yield a yellow solid (200 mg, 86%). 1H-NMR (DMSO-d6) δ 9.08 (s, 1H), 8.54 (m, 3H), 7.92 (dd, 1H), 7.74 (d, 1H), 7.62 (d, 1H), 7.52 (dd, 1H), 7.45 (m, 2H), 7.32 (m, 2H), 7.24 (d, 1H), 7.17 (m, 1H), 5.28 (s, 2H), 3.74 (m, 2H), 3.58 (m, 2H), 2.35 (m, 6H), 1.0 (t, 3H); LCMS RT=3.03 min, [M+H]+=602.0.

Workup

  1. stirringstirred for 10 min at 0° C.
  2. stirringThe resulting mixture was stirred for an additional 5 min at 0° C.
  3. additionwas added to the
  4. temperatureThe resulting mixture were heated at 100° C. for 16 h.
  5. temperatureafter cooled to rt
  6. filtrationThe resulting gel-like mixture was filtered through a pad of Celite® and pad
  7. washwas washed with EtOAc
  8. dry with materialThe combined EtOAc layers were dried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was carefully triturated with ether

Sources & evidence

ORD record
ord-57d439a7bbdb4bc09c01fc6745288175
Source dataset
uspto-grants-2010_07
Patent number
US07750017B2

Reaction notes

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