Potassium Carbonate → HCID 118522334, compound

HRID 529793Notes

Reaction equation

HRID 529793 reaction equation
Br[CH2:2][C:3]([O:5][CH3:6])=[O:4].[NH2:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:44])[CH2:15][N:16]2[CH:20]=[C:19]([NH:21][C:22]([C:24]3[CH:25]=[N:26][N:27]4[CH:32]=[CH:31][CH:30]=[N:29][C:28]=34)=[O:23])[C:18]([C:33]3[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=3[O:40][CH:41]([F:43])[F:42])=[N:17]2)[CH2:10][CH2:9]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:39][C:37]1[CH:36]=[CH:35][C:34]([O:40][CH:41]([F:42])[F:43])=[C:33]([C:18]2[C:19]([NH:21][C:22]([C:24]3[CH:25]=[N:26][N:27]4[CH:32]=[CH:31][CH:30]=[N:29][C:28]=34)=[O:23])=[CH:20][N:16]([CH2:15][C:14]([N:11]3[CH2:10][CH2:9][CH:8]([NH:7][CH2:2][C:3]([O:5][CH3:6])=[O:4])[CH2:13][CH2:12]3)=[O:44])[N:17]=2)[CH:38]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 60984Methyl bromoacetate2×HCID 118522526HCID 118522526, compound

Product 1

HCID 118522334HCID 118522334, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Methyl 2-bromoacetate (30.74 mg, 0.20 mmol) was added to a mixture of N-[1-[2-(4-aminopiperidin-1-yl)-2-oxoethyl]-3-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (100 mg, 0.18 mmol) in DMF (5 mL) and potassium carbonate (38.1 mg, 0.28 mmol). The resulting mixture was stirred at room temperature overnight. Additional amount of methyl 2-bromoacetate (30.74 mg, 0.20 mmol) was added and the resulting solution was stirred at 60° C. for 2 h. The resulting mixture was concentrated under vacuum. The crude product was purified by Prep-HPLC with the following conditions (Prep-HPLC-005): Column, XBridge Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, water with 0.05% FA and MeCN (25.0% MeCN up to 32.0% in 10 min, up to 95.0% in 1 min, hold 95.0% in 1 min, down to 25.0% in 2 min); Detector, UV 254/220 nm. This resulted in 68.9 mg (57%) of the formic acid salt of methyl 2-[[1-(2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]pyrimidine-3-amido]-1H-pyrazol-1-yl]acetyl)piperidin-4-yl]amino]-acetate as an off-white solid. LCMS (Method 24) [M+H]+=617.2, RT=1.53 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.75 (s, 1H), 9.34 dd, 1H, J=1.6, 7.2 Hz), 8.69-8.67 (m, 2H), 8.30 (s, 1H), 7.62 (dd, 1H, J=2.4, 8.8 Hz), 7.55 (d, 1H, J=2.8 Hz), 7.45 (d, 1H, J=8.8 Hz), 7.28 (dd, 1H, J=4.0, 6.8 Hz), 7.08 (t, 1H, J=73.2 Hz), 5.23-5.20 (m, 2H), 4.11-4.07 (m, 1H), 3.83-3.80 (m, 1H), 3.63 (s, 3H), 3.39-3.31 (m, 2H), 3.15-3.12 (m, 1H), 2.87-2.83 (m, 1H), 2.71-2.67 (m, 1H), 1.83-1.77 (m, 2H), 1.29-1.14 (m, 2H).

Workup

  1. stirringthe resulting solution was stirred at 60° C. for 2 h
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. customThe crude product was purified by Prep-HPLC with the following conditions (Prep-HPLC-005)
  4. waitmobile phase, water with 0.05% FA and MeCN (25.0% MeCN up to 32.0% in 10 min
  5. waitup to 95.0% in 1 min
  6. customin 1 min
  7. waitdown to 25.0% in 2 min)

Sources & evidence

ORD record
ord-e2240aaa37e2408f940ae249ec55a642
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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