Ammonia → HCID 59024133, compound

HRID 1678231Notes

Reaction equation

HRID 1678231 reaction equation
C[O:2][C:3]([C:5]1[S:24][C:8]2[N:9]=[C:10]([NH2:23])[N:11]=[C:12]([NH:13][C:14]3[CH:15]=[C:16]4[C:20](=[CH:21][CH:22]=3)[NH:19][N:18]=[CH:17]4)[C:7]=2[CH:6]=1)=O.[NH3:25]>>[NH2:23][C:10]1[N:11]=[C:12]([NH:13][C:14]2[CH:15]=[C:16]3[C:20](=[CH:21][CH:22]=2)[NH:19][N:18]=[CH:17]3)[C:7]2[CH:6]=[C:5]([C:3]([NH2:25])=[O:2])[S:24][C:8]=2[N:9]=1

Participants

3

Reactant 2

HCID 222Ammonia3×HCID 59023751HCID 59023751, compound

Product 1

HCID 59024133HCID 59024133, compoundYield 31%

Conditions

Temperature
60 °C

Procedure

A mixture of 2-amino-4-(1H-indazol-5-ylamino)-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester (Example #N.7.1, 0.050 g, 0.15 mmol) and ammonia (ca. 7N in methanol, 1.0 mL) was heated at about 60° C. in a sealed vessel for about 1.5 hours. The mixture was allowed to cool to ambient temperature and additional ammonia (ca. 7N in methanol, 5.0 mL) was added. The reaction mixture was then heated at about 75° C. for about 18 hours, cooled to ambient temperature, additional ammonia (ca. 7N in methanol, 2.0 mL) was added, and heating at about 75° C. was continued for about another 3 days. The mixture was concentrated under reduced pressure and the residue 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 2-amino-4-(1H-indazol-5-ylamino)-thieno[2,3-d]pyrimidine-6-carboxylic acid amide (0.015 g, 31%) as a beige solid; RP-HPLC (Table 1, Method a) Rt 0.68 min, m/z (ESI+) 325.9 (M+H)+.

Workup

  1. temperatureto cool to ambient temperature
  2. temperatureThe reaction mixture was then heated at about 75° C. for about 18 hours
  3. temperaturecooled to ambient temperature
  4. temperatureheating at about 75° C.
  5. customwas continued for about another 3 days
  6. concentrationThe mixture was concentrated under reduced pressure
  7. customthe residue 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)

Sources & evidence

ORD record
ord-28026d824f4b4cdeb185baaca8ffc2cd
Source dataset
uspto-grants-2011_08
Patent number
US08008481B2

Reaction notes

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