Ammonia → HCID 59024422, compound

HRID 1678255Notes

Reaction equation

HRID 1678255 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[C:11]3[C:15](=[C:16]([C:18]4[NH:19][C:20]5[C:25]([CH:26]=4)=[CH:24][CH:23]=[CH:22][C:21]=5[C:27](O)=[O:28])[CH:17]=2)[NH:14][N:13]=[CH:12]3)[CH:5]=[CH:4][N:3]=1.C1N=C[N:32](C(N2C=NC=C2)=O)C=1.CN(C)C=O.N>>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[C:11]3[C:15](=[C:16]([C:18]4[NH:19][C:20]5[C:25]([CH:26]=4)=[CH:24][CH:23]=[CH:22][C:21]=5[C:27]([NH2:32])=[O:28])[CH:17]=2)[NH:14][N:13]=[CH:12]3)[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 4

HCID 222AmmoniaHCID 6228DimethylformamideHCID 682631,1'-CarbonyldiimidazoleHCID 59024137HCID 59024137, compound

Product 1

HCID 59024422HCID 59024422, compoundYield 2%

Procedure

A solution of 2-[5-(2-amino-pyrimidin-4-ylamino)-1H-indazol-7-yl]-1H-indole-7-carboxylic acid (Example #F.5.11, 0.100 g, 0.000259 mol) and N,N-carbonyldiimidazole (0.0842 g, 0.000519 mol) in N,N-dimethylformamide (2.5 mL, 0.032 mol) was heated at about 55° C. for about 45 min. The mixture was cooled with an ice bath and treated with ammonia gas for about 15 min at about 0° C. The mixture was sealed and allowed to warm to ambient temperature. After about 1 hour the mixture was opened to atmosphere, and a 1.2 mL portion of the mixture was purified by reverse phase 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; 5-50% CH3CN/50 mM aqueous ammonium acetate over 20 min; 50-100% CH3CN/50 mM aqueous ammonium acetate over 1 min; hold at 100% CH3CN for 5 minutes, 21 mL/min) then filtered to remove the remaining acid. The filtrate was then lyophilized to yield 2-[5-(2-amino-pyrimidin-4-ylamino)-1H-indazol-7-yl]-1H-indole-7-carboxylic acid amide (2 mg, 2% yield): LC/MS Rt (Method e) 0.7 min; m/z (M+H)+ 385.4.

Workup

  1. customwas heated at about 55° C. for about 45 min
  2. temperatureThe mixture was cooled with an ice bath
  3. customThe mixture was sealed
  4. customa 1.2 mL portion of the mixture was purified by reverse phase 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; 5-50% CH3CN/50 mM aqueous ammonium acetate over 20 min; 50-100% CH3CN/50 mM aqueous ammonium acetate over 1 min; hold at 100% CH3CN for 5 minutes, 21 mL/min)
  5. filtrationthen filtered
  6. customto remove the remaining acid

Sources & evidence

ORD record
ord-7b38d7fc02d64640b5bfed6bf0d93f63
Source dataset
uspto-grants-2011_08
Patent number
US08008481B2

Reaction notes

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