Ammonia → HCID 73053997, compound

HRID 75315Notes

Reaction equation

HRID 75315 reaction equation
[NH3:1].Cl[C:3]1[N:8]=[C:7]([NH:9][C@H:10]([C:12]2[N:17]=[C:16]3[CH:18]=[CH:19][N:20]([CH3:21])[C:15]3=[CH:14][C:13]=2[C:22]2[N:26]([CH3:27])[N:25]=[CH:24][CH:23]=2)[CH3:11])[C:6]([Cl:28])=[CH:5][N:4]=1.[OH-].[NH4+]>CO>[Cl:28][C:6]1[C:7]([NH:9][C@H:10]([C:12]2[N:17]=[C:16]3[CH:18]=[CH:19][N:20]([CH3:21])[C:15]3=[CH:14][C:13]=2[C:22]2[N:26]([CH3:27])[N:25]=[CH:24][CH:23]=2)[CH3:11])=[N:8][C:3]([NH2:1])=[N:4][CH:5]=1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 14923Ammonium HydroxideHCID 86708018(S)-2,5-dichloro-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)pyrimidin-4-amine

Product 1

HCID 73053997HCID 73053997, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 7 N solution of ammonia (1 mL, 7.00 mmol) in MeOH was added to (S)-2,5-dichloro-N-(1-(1-methyl-6-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)pyrimidin-4-amine (20 mg, 0.050 mmol) while stirring at room temperature. The reaction mixture was stirred at room temperature for 1 hour and then at 100° C. in a microwave reactor for 1 hour. The mixture was concentrated, dissolved in dioxane (1 mL), and treated with ammonium hydroxide (1 mL, 7.19 mmol). The mixture was heated at 100° C. in a microwave reactor for 12 hours. The reaction was concentrated and purified by preparative HPLC (basic mode, 25% to 50% ACN/water gradient) to give the title compound as an off-white solid (13.7 mg, 72.0%). 1H NMR (500 MHz, CD3OD) δ ppm 1.42 (d, J=6.35 Hz, 3 H), 3.66 (s, 3 H), 3.90 (s, 3 H), 5.46 (q, J=6.51 Hz, 1 H), 6.45-6.49 (m, 1 H), 6.69-6.72 (m, 1 H), 7.65 (d, J=2.93 Hz, 2 H), 7.69 (s, 1 H), 7.84 (s, 1 H); ESI-MS m/z [M+H]+ calc'd for C18H19ClN8, 383.14; found 383.3.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 1 hour
  2. concentrationThe mixture was concentrated
  3. dissolutiondissolved in dioxane (1 mL)
  4. temperatureThe mixture was heated at 100° C. in a microwave reactor for 12 hours
  5. concentrationThe reaction was concentrated
  6. custompurified by preparative HPLC (basic mode, 25% to 50% ACN/water gradient)

Sources & evidence

ORD record
ord-f078739f414c4684a7dd9a779cc998cc
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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