3-Aminopropionitrile → HCID 118522810, compound

HRID 529851Notes

Reaction equation

HRID 529851 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:34][CH:35]([F:37])[F:36])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][N:10]([CH2:25][CH:26]=[C:27]3[CH2:32][CH2:31][C:30](=O)[CH2:29][CH2:28]3)[N:9]=2)[CH:7]=1.[NH2:38][CH2:39][CH2:40][C:41]#[N:42].[BH3-]C#N.[Na+]>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:34][CH:35]([F:37])[F:36])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][N:10]([CH2:25][CH:26]=[C:27]3[CH2:28][CH2:29][CH:30]([NH:42][CH2:41][CH2:40][C:39]#[N:38])[CH2:31][CH2:32]3)[N:9]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 16473-AminopropionitrileHCID 5003444Sodium cyanoborohydrideHCID 118522783HCID 118522783, compound

Product 1

HCID 118522810HCID 118522810, compoundYield 2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To solution of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-(4-oxocyclohexylidene)ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (300.0 mg, 0.569 mmol) in methanol (30 mL) was added 3-aminopropanenitrile (199.5 mg, 2.85 mmol). The resulting solution was stirred at room temperature for 3. Then NaBH3CN (71.56 mg, 1.14 mmol) was added. The resulting solution was stirred at room temperature overnight and concentrated under vacuum. The residue was applied onto a short pad of silica gel eluting with ethyl acetate. The crude product (60 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ACN/0.05% NH4HCO3=30% increasing to ACN/0.05% NH4HCO3=55% within 8 min; Detector, UV 254 nm. 6.7 mg product was obtained. This resulted in 6.7 mg (2%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-(2-[4-[(2-cyanoethyl)amino]cyclohexylidene]ethyl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a off-white solid. LCMS (Method 34) [M+H]+=581.4, RT=2.44 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.73 (s, 1H), 9.33 (dd, 1H, J=1.5, 6.9 Hz), 8.68-8.66 (m, 2H), 8.27 (s, 1H), 7.64-7.60 (m, 2H), 7.43 (d, 1H, J=8.1 Hz), 7.27 (dd, 1H, J=4.2, 6.9 Hz), 7.00 (t, 1H, J=73.5 Hz), 5.45 (t, 1H, J=6.9 Hz), 4.80 (d, 2H, J=7.2 Hz), 2.79-2.72 (m, 3H), 2.71-2.57 (m, 5H), 2.10-1.97 (m, 2H), 1.94-1.86 (m, 2H), 1.23-1.16 (m, 2H).

Workup

  1. stirringThe resulting solution was stirred at room temperature overnight
  2. concentrationconcentrated under vacuum
  3. customThe crude product (60 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1)
  4. temperaturemobile phase, ACN/0.05% NH4HCO3=30% increasing to ACN/0.05% NH4HCO3=55% within 8 min

Sources & evidence

ORD record
ord-a070e057d23842ac8c41ec8519bcae3f
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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