Hydrochloric Acid → HCID 59023832, compound

HRID 1678233Notes

Reaction equation

HRID 1678233 reaction equation
C([O-])([O-])=[O:2].C([O-])([O-])=O.OO.OO.OO.[Na+].[Na+].[Na+].[Na+].[NH2:19][C:20]1[N:21]=[C:22]([NH:31][C:32]2[CH:33]=[C:34]3[C:38](=[C:39]([C:41]4[S:45][C:44]5[CH:46]=[CH:47][CH:48]=[CH:49][C:43]=5[CH:42]=4)[CH:40]=2)[NH:37][N:36]=[CH:35]3)[C:23]2[C:28]([C:29]#[N:30])=[CH:27][NH:26][C:24]=2[N:25]=1.NC1N=C2N=CN(C#N)C(Cl)=C2C=1.O=P(Cl)(Cl)Cl.Cl>[OH-].[K+]>[NH2:19][C:20]1[N:21]=[C:22]([NH:31][C:32]2[CH:33]=[C:34]3[C:38](=[C:39]([C:41]4[S:45][C:44]5[CH:46]=[CH:47][CH:48]=[CH:49][C:43]=5[CH:42]=4)[CH:40]=2)[NH:37][N:36]=[CH:35]3)[C:23]2[C:28]([C:29]([NH2:30])=[O:2])=[CH:27][NH:26][C:24]=2[N:25]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 24813Phosphorus oxychlorideHCID 159762Sodium percarbonateHCID 59023744HCID 59023744, compoundHCID 86616743HCID 86616743, compound

Product 1

HCID 59023832HCID 59023832, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 14797Potassium HydroxideSolvent

Procedure

Sodium percarbonate (0.040 g, 0.25 mmol) was added to a mixture of 2-amino-4-(7-benzo[b]thiophen-2-yl-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (prepared via General Procedure N from the reaction of Example #F.8.1 with 6-amino-4-chloro-3-cyano-pyrrolo[2,3-d]pyrimidine [prepared by chlorination of the 4-oxo derivative (J. Med. Chem., 2001, 44(12), 1993-2003) using POCl3 (Tet., 2004, 60, 943-959), 0.10 g, 0.24 mmol) in 1N KOH (2.4 mL) at ambient temperature. After about 21 hours, the reaction mixture was acidified with 5N HCl and filtered. The resulting solid was purified by preparative HPLC (Thermo Hypersil-Keystone 250×21.2 mm 8μ Hypersil® HS C18 column; 5% CH3CN/50 mM aqueous ammonium acetate hold for 5 min, 5-100% CH3CN/50 mM aqueous ammonium acetate over 30 min, hold at 100% CH3CN for 5 minutes, 21 mL/min) to give an impure solid that was triturated with heptane and filtered to give 2-amino-4-(7-benzo[b]thiophen-2-yl-1H-indazol-5-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (6.9 mg, 7%); RP-HPLC (Table 1, Method e) Rt 1.64 min; m/z (ESI+): 441.0 (M+H)+.

Workup

  1. customat ambient temperature
  2. filtrationfiltered
  3. customThe resulting solid was purified by preparative HPLC (Thermo Hypersil-Keystone 250×21.2 mm 8μ Hypersil® HS C18 column; 5% CH3CN/50 mM aqueous ammonium acetate hold for 5 min, 5-100% CH3CN/50 mM aqueous ammonium acetate over 30 min, hold at 100% CH3CN for 5 minutes, 21 mL/min)
  4. customto give an impure solid
  5. customthat was triturated with heptane
  6. filtrationfiltered

Sources & evidence

ORD record
ord-a9b5a1e6a0254a74a623a0a270040d8f
Source dataset
uspto-grants-2011_08
Patent number
US08008481B2

Reaction notes

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