Diisopropylethylamine → HCID 118522937, compound

HRID 529810Notes

Reaction equation

HRID 529810 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([O:36][CH:37]([F:39])[F:38])=[C:13]([C:15]2[C:19]([NH:20][C:21]([C:23]3[CH:24]=[N:25][N:26]4[CH:31]=[CH:30][CH:29]=[N:28][C:27]=34)=[O:22])=[CH:18][N:17]([CH2:32][C:33](O)=[O:34])[N:16]=2)[CH:14]=1.Cl.[N:41]1([CH:47]2[CH2:52][CH2:51][O:50][C:49](=[O:53])[CH2:48]2)[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([O:36][CH:37]([F:39])[F:38])=[C:13]([C:15]2[C:19]([NH:20][C:21]([C:23]3[CH:24]=[N:25][N:26]4[CH:31]=[CH:30][CH:29]=[N:28][C:27]=34)=[O:22])=[CH:18][N:17]([CH2:32][C:33](=[O:34])[N:44]3[CH2:43][CH2:42][N:41]([CH:47]4[CH2:52][CH2:51][O:50][C:49](=[O:53])[CH2:48]4)[CH2:46][CH2:45]3)[N:16]=2)[CH:14]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118522994HCID 118522994, compoundHCID 118523105HCID 118523105, compound

Product 1

HCID 118522937HCID 118522937, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of {3-(5-Chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}acetic acid trifluoroacetate (100 mg, 0.17 mmol) in DMF (3 mL) was added 4-(piperazin-1-yl)oxan-2-one hydrochloride (76 mg, 0.34 mmol), DIEA (67.2 mg, 0.52 mmol), HATU (79.2 mg, 0.21 mmol). The resulting solution was stirred at room temperature overnight and 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 (35.0% up to 39.0% in 10 min, up to 95.0% in 1 min, hold 95.0% in 1 min, down to 35.0% in 2 min); Detector, UV 254/220 nm. This resulted in 14.5 mg (13%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-oxo-2-[4-(2-oxooxan-4-yl)piperazin-1-yl]ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a white solid. LCMS (Method 28) [M+H]+=629.1, RT=1.44 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.76 (s, 1H), 9.34 (dd, 1H, J=2.0, 7.2 Hz), 8.69-8.68 (m, 2H), 8.31 (s, 1H), 7.62 (dd, 1H, J=2.8, 8.8 Hz), 7.55 (d, 1H, J=2.8 Hz), 7.45 (d, 1H, J=8.8 Hz), 7.28 (dd, 1H, J=4.4, 7.2 Hz), 7.08 (t, 1H, J=73.2 Hz), 5.24 (s, 2H), 4.35-4.29 (m, 1H), 4.19-4.16 (m, 1H), 3.50-3.32 (m, 6H), 3.02-2.99 (m, 1H), 2.69-2.51 (m, 4H), 2.08-1.98 (m, 1H), 1.77-1.75 (m, 1H).

Workup

  1. concentrationconcentrated 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 (35.0% up to 39.0% in 10 min
  4. waitup to 95.0% in 1 min
  5. customin 1 min
  6. waitdown to 35.0% in 2 min)
  7. customThis resulted in 14.5 mg (13%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-oxo-2-[4-(2-oxooxan-4-yl)piperazin-1-yl]ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a white solid

Sources & evidence

ORD record
ord-f2b86026257c4e43acd4b6707823e0f8
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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