Formaldehyde → HCID 59285260, compound

HRID 906448Notes

Reaction equation

HRID 906448 reaction equation
[CH:1]1([NH:4][C:5](=[O:38])[C:6]2[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[C:20](=[O:24])[N:19]([CH2:25][CH:26]3[CH2:28][CH2:27]3)[CH:18]=[C:17]4[S:29]([N:32]3[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]3)(=[O:31])=[O:30])[CH:7]=2)[CH2:3][CH2:2]1.C=O.[C:41](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(Cl)Cl>C(O)(=O)C.ClCCCl>[CH:1]1([NH:4][C:5](=[O:38])[C:6]2[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][CH:23]=3)[C:20](=[O:24])[N:19]([CH2:25][CH:26]3[CH2:28][CH2:27]3)[CH:18]=[C:17]4[S:29]([N:32]3[CH2:37][CH2:36][N:35]([CH3:41])[CH2:34][CH2:33]3)(=[O:31])=[O:30])[CH:7]=2)[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 6344DichloromethaneHCID 5049666Sodium triacetoxyborohydrideHCID 59285251HCID 59285251, compound

Product 1

HCID 59285260HCID 59285260, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 111,2-DichloroethaneSolvent

Procedure

Acetic acid (3 drops) was added to a mixture of N-cyclopropyl-3-[2-(cyclopropylmethyl)-1-oxo-4-(piperazin-1-ylsulfonyl)-1,2-dihydroisoquinolin-6-yl]-5-fluoro-4-methylbenzamide (Example 47d, 0.047 g) and paraformaldehyde (7.9 mg) in 1,2-dichloroethane (1 mL). The mixture was stirred at room temperature overnight then sodium triacetoxyborohydride (18.5 mg) was added and the reaction stirred at room temperature for 1 h. DCM (10 mL) was added and the solution washed with water (3×10 mL). The organics were dried (MgSO4), filtered and concentrated under reduced pressure then purified by preparative HPLC (Xbridge column using a 95-5% gradient of aqueous trifluoroacetic acid in acetonitrile) then evaporated to dryness. The product was passed through an ion exchange column (StratoSpheres TM SPE PL-HCO3 MP SPE by Polymer Laboratories, eluting with methanol), to give, after triturating with diethyl ether, the title compound (0.032 g) as a white solid.

Workup

  1. stirringthe reaction stirred at room temperature for 1 h
  2. washthe solution washed with water (3×10 mL)
  3. dry with materialThe organics were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customthen purified by preparative HPLC (Xbridge column
  7. customthen evaporated to dryness
  8. washThe product was passed through an ion exchange column (StratoSpheres TM SPE PL-HCO3 MP SPE by Polymer Laboratories, eluting with methanol)
  9. customto give
  10. customafter triturating with diethyl ether

Sources & evidence

ORD record
ord-8103f7a5a1254e73a77effbfc8acf481
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

Loading…