Ammonia methanol → HCID 44625591, compound

HRID 45053Notes

Reaction equation

HRID 45053 reaction equation
[C:1]([N:3]=[C:4]([N:7]1[CH2:12][CH2:11][C:10]([CH2:27][C:28]#[N:29])([N:13]2[CH:17]=[C:16]([C:18]3[C:19]4[CH:26]=[CH:25][NH:24][C:20]=4[N:21]=[CH:22][N:23]=3)[CH:15]=[N:14]2)[CH2:9][CH2:8]1)SC)#[N:2].[NH3:30].CO>N.C(O)(C)C>[C:1]([N:3]=[C:4]([N:7]1[CH2:12][CH2:11][C:10]([CH2:27][C:28]#[N:29])([N:13]2[CH:17]=[C:16]([C:18]3[C:19]4[CH:26]=[CH:25][NH:24][C:20]=4[N:21]=[CH:22][N:23]=3)[CH:15]=[N:14]2)[CH2:9][CH2:8]1)[NH2:30])#[N:2]

Participants

5

Reactant 2

HCID 21705897Ammonia methanolHCID 87066468Methyl n-cyano-4-(cyanomethyl)-4-[4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl]-piperidine-1-carbimidothioate

Product 1

HCID 44625591HCID 44625591, compound

Reagents, catalysts & solvents 2

HCID 222AmmoniaSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
100 °C

Procedure

Methyl N-cyano-4-(cyanomethyl)-4-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-piperidine-1-carbimidothioate (41.3 mg, 0.102 mmol) (53 mg TFA salt) was dissolved in 2.0 M ammonia in isopropyl alcohol (4.00 mL). The resulting mixture was heated to 100° C. for 1 h in a microwave reactor. Analysis by HPLC and LCMS showed 60% reaction to give the expected M+H 375 (50 area %). To this mixture was added 2 mL of 7 N NH3/MeOH. The resulting mixture was heated at 120° C. for one hour. HPLC and LCMS analyses showed no remaining starting material. The reaction mixture was concentrated on a rotory evaporator. The product was isolated by prep HPLCMS using a 30 mm×100 mm C18 column, eluting with a solvent gradient; 10% ACN—H2O (0.1% TFA), 1.5 min, to 30% at 6 min; 60 mL/min; detector set at m/z 375; retention time, 4.7 min. The eluate was freeze-dried to yield 11.7 mg of the product TFA salt as a white solid. 1H NMR (d6-DMSO) δ 12.69 (s, 1H, NH); 8.92 (s, 1H); 8.81 (s, 1H); 8.51 (s, 1H); 7.75 (m, 1H); 7.22 (m, 1H); 7.18 (s, 2H, NH2); 3.84 (m, 2H); 3.23 (s, 2H); 2.99 (m, 2H); 2.60 (m, 2H); 1.97 (m, 2H). MS(ES) 375 (M+H).

Workup

  1. custom60% reaction
  2. customto give the expected M+H 375 (50 area %)
  3. temperatureThe resulting mixture was heated at 120° C. for one hour
  4. concentrationThe reaction mixture was concentrated on a rotory evaporator
  5. customThe product was isolated by prep HPLCMS
  6. washeluting with a solvent gradient
  7. customretention time, 4.7 min
  8. customThe eluate was freeze-dried

Sources & evidence

ORD record
ord-3775716fb1664200afab021e0ae85792
Source dataset
uspto-grants-2013_09
Patent number
US08541425B2

Reaction notes

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