Tetrahydro-4H-pyran-4-one → HCID 118522560, compound

HRID 529854Notes

Reaction equation

HRID 529854 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([O:38][CH:39]([F:41])[F:40])=[C:7]([C:9]2[C:13]([NH:14][C:15]([C:17]3[CH:18]=[N:19][N:20]4[CH:25]=[CH:24][CH:23]=[N:22][C:21]=34)=[O:16])=[CH:12][N:11]([CH2:26][C:27]3[N:28]=[N:29][N:30]([CH:32]4[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]4)[CH:31]=3)[N:10]=2)[CH:8]=1.[O:42]1[CH2:47][CH2:46][C:45](=O)[CH2:44][CH2:43]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(#N)C.O>ClCCl>[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([O:38][CH:39]([F:41])[F:40])=[C:7]([C:9]2[C:13]([NH:14][C:15]([C:17]3[CH:18]=[N:19][N:20]4[CH:25]=[CH:24][CH:23]=[N:22][C:21]=34)=[O:16])=[CH:12][N:11]([CH2:26][C:27]3[N:28]=[N:29][N:30]([CH:32]4[CH2:33][CH2:34][N:35]([CH:45]5[CH2:46][CH2:47][O:42][CH2:43][CH2:44]5)[CH2:36][CH2:37]4)[CH:31]=3)[N:10]=2)[CH:8]=1

Participants

6

Reactant 4

HCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 18373917Acetonitrile--water (1/1)2×HCID 118522687HCID 118522687, compound

Product 1

HCID 118522560HCID 118522560, compoundYield 26.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[[1-(piperidin-4-yl)-1H-1,2,3-triazol-4-yl]methyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide hydrochloride (200 mg, 0.330 mmol) in dichloromethane (30 mL) was added oxan-4-one (264.9 mg, 2.646 mmol). The resulting solution was stirred at room temperature overnight. Then NaBH(OAc)3 (280.8 mg, 1.325 mmol) was added. The resulting solution was stirred at room temperature for 6 h and concentrated under vacuum. The residue was applied onto a silica gel column eluting with DCM/MeOH (80:20). The crude product (150 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ACN/H2O (10 mmol NH4HCO3)=20% increasing to ACN/H2O (10 mmol NH4HCO3)=49% within 8 min; Detector, UV 254 nm. 56.9 mg product was obtained. This resulted in 56.9 mg (26%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-([1-[1-(oxan-4-yl)piperidin-4-yl]-1H-1,2,3-triazol-4-yl]methyl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a light yellow solid. LCMS (Method 20) [M+H]+=653.3, RT=1.74 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.73 (s, 1H), 9.34 (dd, 1H, J=1.6, 7.2 Hz), 8.67-8.66 (m, 2H), 8.39 (s, 1H), 8.26 (s, 1H), 7.65-7.62 (m, 2H), 7.44 (d, 1H, J=8.4 Hz), 7.28 (dd, 1H, J=4.0, 6.8 Hz), 7.06 (t, 1H, J=73.4 Hz), 5.48 (s, 2H), 4.58-4.45 (m, 1H), 3.90-3.87 (m, 2H), 3.32-3.25 (m, 2H), 3.04-2.98 (m, 2H), 2.51-2.33 (m, 1H), 2.30-2.24 (m, 2H), 2.09-2.06 (m, 2H), 1.99-1.91 (m, 2H), 1.70-1.67 ((m, 2H), 1.49-1.40 (m, 2H).

Workup

  1. stirringThe resulting solution was stirred at room temperature for 6 h
  2. concentrationconcentrated under vacuum
  3. washeluting with DCM/MeOH (80:20)
  4. customThe crude product (150 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1)

Sources & evidence

ORD record
ord-e2221bac7af145178e1c1c8f0e7070eb
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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