Isopropanol → HCID 11256634, compound

HRID 1160110Notes

Reaction equation

HRID 1160110 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)=[O:11])[C:5]([CH:23]=O)=[C:4](Cl)[N:3]=1.C(O)(C)C.O.[NH2:31][NH2:32]>O>[NH2:1][C:2]1[N:3]=[C:4]2[NH:31][N:32]=[CH:23][C:5]2=[C:6]([NH:8][CH2:9][C:10]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)=[O:11])[N:7]=1

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 24654Hydrazine hydrate (1:1)2×HCID 112917662-(2-Amino-6-chloro-5-formyl-pyrimidin-4-ylamino)-N-(3-trifluoromethyl-phenyl)-acetamide

Product 1

HCID 11256634HCID 11256634, compoundYield 34.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

In a disposable sealed tube was added 2-(2-Amino-6-chloro-5-formyl-pyrimidin-4-ylamino)-N-(3-trifluoromethyl-phenyl)-acetamide (96.0 mg, 0.25 mmol, 1.0 eq.), isopropanol (2.0 mL), and hydrazine monohydrate (0.02 mL, 0.35 mmol, 1.4 eq.). The reaction was sealed and heated to 80° C. After 2 hrs, the reaction was spiked with 0.01 mL of hydrazine monohydrate, resealed, and allowed to continue stirring at 80° C. overnight. The reaction was then cooled to RT and the resulting yellow precipitate was filtered and rinsed with cold EtOH to give crude 2-(6-amino-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)-N-(3-trifluoromethyl-phenyl)-acetamide. The crude precipitate was then sonicated in 1.0 mL H2O, filtered, rinsed with an additional 1 mL H2O, and lyophilized overnight to give pure 2-(6-amino-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)-N-(3-trifluoromethyl-phenyl)-acetamide as a pale yellow solid (30 mg, 34%). LC/MSD (HP Series 1100 MSD): Expected MW: 351, Observed M+H, 352.1, Retention time: 1.19 min. ANALYTICAL HPLC: >90%, Retention time: 3.58 min (8 minute run). 1H-NMR (d6-DMSO): 12.5 (br s, 1H), 10.42 (s, 1H), 8.15 (s, 1H), 7.80 (m, 2H), 7.59 (t, 1H), 7.41 (d, 1H), 6.01 (br s, 2H), 4.40 (rotamer d, 2H) ppm.

Workup

  1. customThe reaction was sealed
  2. temperatureThe reaction was then cooled to RT
  3. filtrationthe resulting yellow precipitate was filtered
  4. washrinsed with cold EtOH
  5. customto give crude 2-(6-amino-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)-N-(3-trifluoromethyl-phenyl)-acetamide
  6. filtrationfiltered
  7. washrinsed with an additional 1 mL H2O
  8. waitlyophilized overnight

Sources & evidence

ORD record
ord-b041e04c1c524900963bc5e5c12d1ccb
Source dataset
uspto-grants-2010_10
Patent number
US07816353B2

Reaction notes

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