Dichloromethane → HCID 58346419, compound

HRID 222034Notes

Reaction equation

HRID 222034 reaction equation
ClCCl.[Cl:4][C:5]1[CH:6]=[C:7]([NH:19][C:20]2[C:25]3[C:26]4[CH2:34][CH2:33][C:32]5[N:31]([CH2:35][CH2:36]O)[N:30]=[CH:29][C:28]=5[C:27]=4[S:38][C:24]=3[N:23]=[CH:22][N:21]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1.S(Br)([Br:41])=O>O>[Br:41][CH2:36][CH2:35][N:31]1[C:32]2[CH2:33][CH2:34][C:26]3[C:25]4[C:24](=[N:23][CH:22]=[N:21][C:20]=4[NH:19][C:7]4[CH:8]=[CH:9][C:10]([O:11][CH2:12][C:13]5[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=5)=[C:5]([Cl:4])[CH:6]=4)[S:38][C:27]=3[C:28]=2[CH:29]=[N:30]1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 68176Thionyl bromideHCID 58346589HCID 58346589, compound

Product 1

HCID 58346419HCID 58346419, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To 30 mL dichloromethane cooled to 0° C. was added 2-(6-{[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}-4,5-dihydro-3H-pyrimido[5′,4′:4,5]thieno[2,3-e]indazol-3-yl)ethanol (800 mg, 1.58 mmol), followed by thionyl bromide (1.15 g, 5.54 mmol). The contents were then stirred with warming to rt over a 24 h period, after which time water (5 mL) was added to quench the reaction mixture. The solvent was removed under reduced pressure. The crude residue was diluted with aq. 1M Na2CO3 and vigorously stirred for 1 h. The mixture was extracted with CH2Cl2, and the combined organic layers dried over MgSO4, filtered, and concentrated in vacuo. The resulting solid was triturated with methanol (15 mL) to a light-brown solid (600 mg, 67%) containing 80% of the desired product, and 20% of the aromatized product. A sample of the crude product was purified via reverse phase HPLC to afford the desired product as a white solid. 1H-NMR (DMSO-d6) δ 8.58 (d, 1H), 8.38 (br s, 1H), 8.36 (s, 1H), 7.81 (dd, 1H), 7.78 (s, 1H), 7.70 (s, 1H), 7.44-7.60 (m, 2H), 7.31 (td, 1H), 7.19 (d, 1H), 5.23 (s, 2H), 4.30 (t, 2H), 3.82 (t, 2H), 3.38 (t, 2H), 3.07 (t, 2H); LCMS RT=2.77 min; [M+H]+=567.0.

Workup

  1. customto quench the reaction mixture
  2. customThe solvent was removed under reduced pressure
  3. additionThe crude residue was diluted with aq. 1M Na2CO3
  4. stirringvigorously stirred for 1 h
  5. extractionThe mixture was extracted with CH2Cl2
  6. dry with materialthe combined organic layers dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting solid was triturated with methanol (15 mL) to a light-brown solid (600 mg, 67%)
  10. additioncontaining 80% of the desired product, and 20% of the aromatized product
  11. customA sample of the crude product was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-15196c6bf5cf4295a48ff24272bae8cc
Source dataset
uspto-grants-2012_06
Patent number
US08207172B2

Reaction notes

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