Formaldehyde → (S)-9-(4-(1-(dimethylamino)propan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one Hydrochloride

HRID 1853704Notes

Reaction equation

HRID 1853704 reaction equation
[ClH:1].N[CH2:3][C@H:4]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:13]3[C:14]4[CH:28]=[CH:27][S:26][C:15]=4[C:16](=[O:25])[NH:17][C:18]=3[C:19]([CH3:24])=[CH:20][C:21]=2[O:22][CH3:23])=[CH:8][C:7]=1[F:29])[CH3:5].[CH2:30]=O.[BH3-][C:33]#[N:34].[Na+]>CO.C1COCC1>[ClH:1].[CH3:30][N:34]([CH3:33])[CH2:3][C@H:4]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:13]3[C:14]4[CH:28]=[CH:27][S:26][C:15]=4[C:16](=[O:25])[NH:17][C:18]=3[C:19]([CH3:24])=[CH:20][C:21]=2[O:22][CH3:23])=[CH:8][C:7]=1[F:29])[CH3:5]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 86689468(S)-9-(4-(1-aminopropan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

Product 1

HCID 86689467(S)-9-(4-(1-(dimethylamino)propan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one HydrochlorideYield 60.6%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of (S)-9-(4-(1-aminopropan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one hydrochloride (110 mg, 0.27 mmol)) in a 1:1 mixture of MeOH/THF (3 mL) was added paraformaldehyde (7.5 mg, 0.24 mmol) followed by NaCNBH3 (70 mg 1.2 mmol) and stirred at rt for 16 h. The reaction mixture was quenched by the addition of 2 N NaHCO3 (1 mL), eluted through an SCX ion-exchange column and converted to HCl salt using General Procedure D-2 (Scheme II) to obtain the desired product (67 mg, 60%) as a white solid: ESI MS m/z 425 [C24H25FN2O2S+H]+;

Workup

  1. customThe reaction mixture was quenched by the addition of 2 N NaHCO3 (1 mL)
  2. washeluted through an SCX ion-exchange column

Sources & evidence

ORD record
ord-df7b7d5c753049af9410ca763c2a13bf
Source dataset
uspto-grants-2015_02
Patent number
US08962648B2

Reaction notes

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