Diisopropylethylamine → HCID 118522817, compound

HRID 529807Notes

Reaction equation

HRID 529807 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:36][CH:37]([F:39])[F:38])=[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][C:26]([N:28]3[CH2:33][CH2:32][CH:31]([NH:34][CH3:35])[CH2:30][CH2:29]3)=[O:27])[N:9]=2)[CH:7]=1.CCN(C(C)C)C(C)C.FC(F)(F)S(O[CH2:55][CH:56]1[CH2:60][CH2:59][C:58](=[O:61])[O:57]1)(=O)=O>CC#N>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:36][CH:37]([F:38])[F:39])=[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][C:26]([N:28]3[CH2:29][CH2:30][CH:31]([N:34]([CH3:35])[CH2:55][CH:56]4[CH2:60][CH2:59][C:58](=[O:61])[O:57]4)[CH2:32][CH2:33]3)=[O:27])[N:9]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 87677882HCID 87677882, compoundHCID 118522710HCID 118522710, compound

Product 1

HCID 118522817HCID 118522817, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[4-(methylamino)piperidin-1-yl]-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (100 mg, 0.18 mmol) in CH3CN (5 mL) was added DIEA (70 mg, 0.54 mmol) and (5-oxooxolan-2-yl)methyl trifluoromethanesulfonate (66.5 mg, 0.27 mmol). The resulting solution was stirred overnight at room temperature. 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 (30.0% up to 36.0% in 10 min, up to 95.0% in 1 min, hold 95.0% in 1 min, down to 30.0% in 2 min); Detector, UV 254/220 nm. This resulted in 37 mg (31%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-(4-[methyl[(5-oxooxolan-2-yl)methyl]amino]piperidin-1-yl)-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a yellow solid. LCMS (Method 24) [M+H]+=657.2, RT=1.68 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.75 (s, 1H), 9.34 (dd, 1H, J=1.2, 7.2 Hz), 8.69-8.68 (m, 2H), 8.31 (s, 1H), 7.62 (dd, 1H, J=2.4, 8.8 Hz), 7.55 (d, 1H, J=2.8 Hz), 7.46 (d, 1H, J=8.8 Hz), 7.29 (dd, 1H, J=4.0, 6.8 Hz), 7.09 (t, 1H, J=73.2 Hz), 5.24-5.17 (m, 2H), 4.58-4.54 (m, 1H), 4.41-4.38 (m, 1H), 3.98-3.95 (m, 1H), 3.16-3.03 (m, 1H), 2.69-2.55 (m, 4H), 2.46-2.44 (m, 2H), 2.26 (s, 3H), 2.24-2.16 (m, 1H), 1.88-1.83 (m, 1H), 1.79-1.71 (m, 2H), 1.48-1.44 (m, 1H), 1.29-1.21 (m, 1H).

Workup

  1. customThe crude product was purified by Prep-HPLC with the following conditions (Prep-HPLC-005)
  2. waitmobile phase, water with 0.05% FA and MeCN (30.0% up to 36.0% in 10 min
  3. waitup to 95.0% in 1 min
  4. customin 1 min
  5. waitdown to 30.0% in 2 min)
  6. customThis resulted in 37 mg (31%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-(4-[methyl[(5-oxooxolan-2-yl)methyl]amino]piperidin-1-yl)-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a yellow solid

Sources & evidence

ORD record
ord-d30052b243074640bd02b507aff7d95e
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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