Acetic Acid → HCID 58958113, compound

HRID 2252090Notes

Reaction equation

HRID 2252090 reaction equation
C[C:2]1[CH:11]=[C:10](N)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH3:13][C:14]1[CH:23]=[C:22]([NH:24][C:25]2[CH:26]=[C:27]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([CH:37]=O)[CH:32]=3)[CH:28]=[CH:29][CH:30]=2)[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CC(O)=O>ClC(Cl)C>[CH2:4]1[C:9]2[C:10](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:11][CH2:2][N:3]1[CH2:37][C:33]1[CH:32]=[C:31]([C:27]2[CH:28]=[CH:29][CH:30]=[C:25]([NH:24][C:22]3[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[N:15]=[C:14]([CH3:13])[CH:23]=3)[CH:26]=2)[CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 811164-Amino-2-methylquinolineHCID 5049666Sodium triacetoxyborohydrideHCID 58958219HCID 58958219, compound

Product 1

HCID 58958113HCID 58958113, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

(3-Bromophenyl)-(2-methylquinolin-4-yl)amine (71). 71 is prepared from 70 by the procedure of Example 1 Step 3. Step 2. 3′-(2-Methylquinolin-4-ylamino)biphenyl-3-carbaldehyde (73). To a suspension of 71 (294 mg, 0.94 mmol) in toluene (9.6 mL) under N2 were sequentially added saturated NaHCO3 (aq. 3.8 mL), a solution of 72 (199 mg, 1.33 mmol) in EtOH (6.7 mL), and PdCl2(Ph3P)3 (32 mg, 0.046 mmol). The reaction was heated at 80° C. for 21 hours before it was allowed to cool to room temperature. The reaction mixture was extracted with ethyl acetate (40 mL) and washed with water (15 mL), brine (15 mL). The ethyl acetate extracts were dried over anhydrous magnesium sulfate and concentrated. The residue was chromatographed on silica gel (dichloromethane to 20:1 dichloromethane/methanol) to give 73 as a yellow solid (219 mg, 68.9%). Step 3.3′-(3,4-Dihydro-1H-isoquinolin-2-ylmethyl)biphenyl-3-yl]-(2-methylquinolin-4-yl)amine. To a solution of 73 (102 mg, 0.301 mmol) in dichloroethane (3.0 mL) under N2 was added 40 (0.04 mL, 0.315 mmol). The reaction was stirred for 24 minutes before the sequential addition of NaBH(OAc)3 (94 mg, 0.444 mmol) and AcOH (0.02 mL, 0.349 mmol). The reaction was stirred for 19 hours and then extracted with ethyl acetate (2×30 mL). The ethyl acetate extracts were washed with 2 N NaOH (aq. 15 mL), brine (15 mL), dried (MgSO4), and concentrated. The residue was chromatographed on silica gel (dichloromethane to 30:1 to 20:1dichloromethane/methanol) to give the desired product as a yellow solid (75 mg, 55%).

Workup

  1. extractionextracted with ethyl acetate (2×30 mL)
  2. washThe ethyl acetate extracts were washed with 2 N NaOH (aq. 15 mL), brine (15 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe residue was chromatographed on silica gel (dichloromethane to 30:1 to 20:1dichloromethane/methanol)

Sources & evidence

ORD record
ord-6a3c9f7a25ea4ed78ab35b67fbda0456
Source dataset
uspto-grants-2008_01
Patent number
US07320989B2

Reaction notes

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