Acetaldehyde → HCID 118522689, compound

HRID 529824Notes

Reaction equation

HRID 529824 reaction equation
[NH2:1][C@@H:2]([CH3:32])[CH2:3][N:4]1[CH:8]=[C:7]([NH:9][C:10]([C:12]2[CH:13]=[N:14][N:15]3[CH:20]=[CH:19][CH:18]=[N:17][C:16]=23)=[O:11])[C:6]([C:21]2[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=2[O:28][CH:29]([F:31])[F:30])=[N:5]1.[CH:33](=O)[CH3:34].[BH3-]C#N.[Na+]>CCO>[Cl:27][C:25]1[CH:24]=[CH:23][C:22]([O:28][CH:29]([F:30])[F:31])=[C:21]([C:6]2[C:7]([NH:9][C:10]([C:12]3[CH:13]=[N:14][N:15]4[CH:20]=[CH:19][CH:18]=[N:17][C:16]=34)=[O:11])=[CH:8][N:4]([CH2:3][C@@H:2]([NH:1][CH2:33][CH3:34])[CH3:32])[N:5]=2)[CH:26]=1

Participants

5

Reactant 3

HCID 177AcetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 118522674HCID 118522674, compound

Product 1

HCID 118522689HCID 118522689, compoundYield 11.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of N-[1-[(2S)-2-aminopropyl]-3-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (200 mg, 0.43 mmol) in EtOH (20 mL) was added acetaldehyde (48 mg, 40% aqueous solution) and NaBH3CN (32.7 mg, 0.52 mmol). The resulting solution was stirred at room temperature for 12 h and concentrated under vacuum. The residue was passed through a short pad of silica gel eluting with 5% MeOH in DCM. The crude product (60 mg) was purified by Prep-HPLC with the following conditions (3#-Pre-HPLC-006(Waters)): Column, XSelect CSH Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, Water with 10 mM NH4CO3 and MeCN (26.0% MeCN up to 40.0% in 8 min); Detector, 254/220. 24.2 mg product was obtained. This resulted in 24.2 mg (11%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[(2S)-2-(ethylamino)propyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a light yellow solid. LCMS (Method 28) [M+H]+=490.1, RT=0.86 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.74 (s, 1H), 9.34 (dd, 1H, J=1.6, 7.2 Hz), 8.68-8.67 (m, 2H), 8.34 (s, 1H), 7.64 (d, 1H, J=2.1 Hz), 7.60 (dd, 1H, J=2.8, 8.4 Hz), 7.44 (d, 1H, J=8.4 Hz), 7.28 (dd, 1H, J=4.0, 7.2 Hz), 7.04 (t, 1H, J=73.2 Hz), 4.11 (dd, 1H, J=6.0, 13.6 Hz), 4.01 (dd, 1H, J=6.2, 13.6 Hz), 3.08-3.00 (m, 1H), 2.68-2.50 (m, 2H), 1.52 (br, 1H), 0.97 (t, 3H, J=7.0 Hz), 0.95 (d, 3H, J=6.4 Hz).

Workup

  1. concentrationconcentrated under vacuum
  2. customThe crude product (60 mg) was purified by Prep-HPLC with the following conditions (3#-Pre-HPLC-006(Waters))
  3. waitmobile phase, Water with 10 mM NH4CO3 and MeCN (26.0% MeCN up to 40.0% in 8 min)

Sources & evidence

ORD record
ord-2238157233ac4e57b1e8ed2dd886059b
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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