Morpholine → HCID 118522409, compound

HRID 529843Notes

Reaction equation

HRID 529843 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:30][CH:31]([F:33])[F:32])=[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]/[CH:26]=[CH:27]/[CH2:28]Cl)[N:9]=2)[CH:7]=1.[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:30][CH:31]([F:32])[F:33])=[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]/[CH:26]=[CH:27]/[CH2:28][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[N:9]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 118522401HCID 118522401, compound

Product 1

HCID 118522409HCID 118522409, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[(2E)-4-chlorobut-2-en-1-yl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (160 mg, 0.324 mmol) and morpholine (0.5 mL) in DMF (4 mL) was stirred at room temperature for 2 h. The resulting mixture was concentrated under vacuum. The crude product (200 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, CH3CN/H2O=20% increasing to CH3CN/H2O=50% within 20 min; Detector, UV 254 nm. 35.4 mg product was obtained. This resulted in 35.4 mg (20%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[(2E)-4-(morpholin-4-yl)but-2-en-1-yl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a off-white solid. LCMS (Method 23) [M+H]+=544.0, RT=2.37 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 9.74 (s, 1H), 9.34 (dd, 1H, J=1.6, 6.8 Hz), 8.68-8.66 (m, 2H), 8.31 (s, 1H), 7.62 (dd, 1H, J=2.8, 8.8 Hz), 7.58 (d, 1H, J=2.8 Hz), 7.44 (d, 1H, J=8.8 Hz), 7.28 (dd, 1H, J=4.4, 6.8 Hz), 7.06 (t, 1H, J=73.2 Hz), 5.94-5.84 (m, 1H), 5.79-5.69 (m, 1H), 4.82 (d, 2H, J=6.0 Hz), 3.56 (t, 4H, J=4.6 Hz), 2.96 (d, 2H, J=6.4 Hz), 2.40-2.30 (m, 4H).

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customThe crude product (200 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1)
  3. temperaturemobile phase, CH3CN/H2O=20% increasing to CH3CN/H2O=50% within 20 min

Sources & evidence

ORD record
ord-7e69df9a1ad549c59ff546b3e5532cb4
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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