Hydrochloric Acid → HCID 23650960, compound

HRID 76370Notes

Reaction equation

HRID 76370 reaction equation
[F:1][C:2]1[C:3]([CH3:10])=[C:4]([NH2:9])[C:5]([NH2:8])=[CH:6][CH:7]=1.Cl.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+].[CH3:21][C:22]1[C:27]([CH:28]=O)=[CH:26][N:25]=[C:24]([NH:30][CH2:31][CH2:32][CH2:33][CH:34]2[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]2)[N:23]=1.C(N(CC)CC)C>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]2[NH:8][C:28]([C:27]3[C:22]([CH3:21])=[N:23][C:24]([NH:30][CH2:31][CH2:32][CH2:33][CH:34]4[CH2:35][CH2:36][N:37]([CH3:40])[CH2:38][CH2:39]4)=[N:25][CH:26]=3)=[N:9][C:4]=2[C:3]=1[CH3:10]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 656671Sodium PyrosulfiteHCID 220555474-Fluoro-3-methylbenzene-1,2-diamineHCID 462215604-Methyl-2-((3-(1-methylpiperidin-4-yl)propyl)amino)pyrimidine-5-carbaldehyde

Product 1

HCID 23650960HCID 23650960, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a 2 L Erlenmeyer flask were added 4-fluoro-3-methyl-benzene-1,2-diamine.HCl (46.32 g, 262.3 mmol), Na2S2O5 (64.82 g, 341.0 mmol), and 4-methyl-2-[3-(1-methyl-piperidin-4-yl)-propylamino]-pyrimidine-5-carbaldehyde (72.5 g, 262.3 mmol) in DMF (725 mL). To the resultant mixture was then added triethylamine (36.6 mL, 262.3 mmol), and the reaction was warmed on a hot plate with stirring to 90° C. and held at this temperature for 2 hours. The resultant mixture was then concentrated to near dryness and partitioned between dichloromethane (1 L) and 1 N NaOH (1 L). After separation of the layers, the aqueous layer was extracted a second time with dichloromethane (1 L). The combined organic layers were then washed with saturated aqueous NaHCO3 (1.6 L). The organics were then extracted with a 1 M mono/dibasic phosphate buffer (pH 5.62, 1.23 L). The aqueous layer was then basified with 50% NaOH (80 mL) to pH 10.8. The resultant heterogeneous layer was then extracted with dichloromethane (1.5 L and 500 mL), and the combined organics were concentrated to yield the title compound.

Workup

  1. concentrationThe resultant mixture was then concentrated
  2. custompartitioned between dichloromethane (1 L) and 1 N NaOH (1 L)
  3. customAfter separation of the layers
  4. extractionthe aqueous layer was extracted a second time with dichloromethane (1 L)
  5. washThe combined organic layers were then washed with saturated aqueous NaHCO3 (1.6 L)
  6. extractionThe organics were then extracted with a 1 M mono/dibasic phosphate buffer (pH 5.62, 1.23 L)
  7. extractionThe resultant heterogeneous layer was then extracted with dichloromethane (1.5 L and 500 mL)
  8. concentrationthe combined organics were concentrated

Sources & evidence

ORD record
ord-f76572d9538c405aade718cd1ea1ee32
Source dataset
uspto-grants-2014_09
Patent number
US08835633B2

Reaction notes

Loading…