Diisopropylethylamine → HCID 118522828, compound

HRID 529794Notes

Reaction equation

HRID 529794 reaction equation
CCN(C(C)C)C(C)C.[NH2:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17](=[O:47])[CH2:18][N:19]2[CH:23]=[C:22]([NH:24][C:25]([C:27]3[CH:28]=[N:29][N:30]4[CH:35]=[CH:34][CH:33]=[N:32][C:31]=34)=[O:26])[C:21]([C:36]3[CH:41]=[C:40]([Cl:42])[CH:39]=[CH:38][C:37]=3[O:43][CH:44]([F:46])[F:45])=[N:20]2)[CH2:13][CH2:12]1.FC(F)(F)S(O[CH2:54][CH:55]1[CH2:59][CH2:58][C:57](=[O:60])[O:56]1)(=O)=O>CC#N>[CH:57]([OH:60])=[O:56].[Cl:42][C:40]1[CH:39]=[CH:38][C:37]([O:43][CH:44]([F:45])[F:46])=[C:36]([C:21]2[C:22]([NH:24][C:25]([C:27]3[CH:28]=[N:29][N:30]4[CH:35]=[CH:34][CH:33]=[N:32][C:31]=34)=[O:26])=[CH:23][N:19]([CH2:18][C:17]([N:14]3[CH2:15][CH2:16][CH:11]([N:10]4[CH2:54][CH:55]([OH:56])[CH2:59][CH2:58][C:57]4=[O:60])[CH2:12][CH2:13]3)=[O:47])[N:20]=2)[CH:41]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 87677882HCID 87677882, compoundHCID 118522526HCID 118522526, compound

Product 1

HCID 118522828HCID 118522828, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

DIEA (71 mg, 0.55 mmol) was added to a solution 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) and (5-oxooxolan-2-yl)methyl trifluoromethanesulfonate (69 mg, 0.28 mmol) in CH3CN (30 mL). The resulting solution was stirred overnight at room temperature. 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 (38.0% up to 46.0% in 10 min, up to 95.0% in 1 min, hold 95.0% in 1 min, down to 38.0% in 2 min); Detector, UV 254/220 nm. This resulted in 41.6 mg (33%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[4-(5-hydroxy-2-oxopiperidin-1-yl)piperidin-1-yl]-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as an off-white solid. LCMS (Method 25) [M+H]+=643.2, RT=1.49 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.75 (s, 1H), 9.35 (dd, 1H, J=1.6, 6.8 Hz), 8.69-8.68 (m, 2H), 8.32 (s, 1H), 7.63 (dd, 1H, J=2.8, 8.8 Hz), 7.56 (d, 1H, J=2.8 Hz), 7.46 (d, 1H, J=8.8 Hz), 7.29 (dd, 1H, J=4.4, 7.2 Hz), 7.09 (t, 1H, J=73.2 Hz), 5.26-5.24 (m, 2H), 4.89 (br, 1H), 4.59-4.45 (m, 2H), 4.08-3.90 (m, 2H), 3.25-2.97 (m, 3H), 2.68-2.58 (m, 1H), 2.46-2.21 (m, 2H), 1.86-1.65 (m, 3H), 1.57-1.50 (m, 3H).

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customThe crude product was purified by Prep-HPLC with the following conditions (Prep-HPLC-005)
  3. waitmobile phase, water with 0.05% FA and MeCN (38.0% up to 46.0% in 10 min
  4. waitup to 95.0% in 1 min
  5. customin 1 min
  6. waitdown to 38.0% in 2 min)
  7. customThis resulted in 41.6 mg (33%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[4-(5-hydroxy-2-oxopiperidin-1-yl)piperidin-1-yl]-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as an off-white solid

Sources & evidence

ORD record
ord-0ab0954f1b42466aa07e068ed3971eea
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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