Water → (R)-4-(2-chloro-6-(3-cyclopropyl-1-ethyl-1H-pyrazol-5-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylmorpholine

HRID 80860Notes

Reaction equation

HRID 80860 reaction equation
[Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[CH2:11][N:10]([C:12]3[N:16]([CH3:17])[N:15]=[C:14]([CH:18]4[CH2:20][CH2:19]4)[CH:13]=3)[CH2:9][CH2:8][C:6]=2[N:7]=1.[CH3:22][C@@H:23]1[CH2:28][O:27][CH2:26][CH2:25][NH:24]1.[CH3:29]CN(C(C)C)C(C)C.O>CC(N(C)C)=O>[Cl:1][C:2]1[N:3]=[C:4]([N:24]2[CH2:25][CH2:26][O:27][CH2:28][C@H:23]2[CH3:22])[C:5]2[CH2:11][N:10]([C:12]3[N:16]([CH2:17][CH3:29])[N:15]=[C:14]([CH:18]4[CH2:20][CH2:19]4)[CH:13]=3)[CH2:9][CH2:8][C:6]=2[N:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 641498(R)-3-MethylmorpholineHCID 86690295HCID 86690295, compound

Product 1

HCID 86690294(R)-4-(2-chloro-6-(3-cyclopropyl-1-ethyl-1H-pyrazol-5-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylmorpholine

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 2,4-dichloro-6-(3-cyclopropyl-1-methyl-1H-pyrazol-5-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (0.110 g, 0.325 mmol) in DMA (2.2 mL) was added (R)-3-methylmorpholine (49.3 mg, 0.488 mmol) and DIPEA (284 μL, 1.63 mmol). The mixture was heated at 110° C. for 2 h. Water was added and the aqueous phase was extracted with EtOAc (3×). The organic phases were combined, washed with brine (3×), dried with sodium sulfate, filtered and concentrated under reduce pressure. Purification by FCC (0-60% EtOAc/heptane) provided the title compound (R)-4-(2-chloro-6-(3-cyclopropyl-1-ethyl-1H-pyrazol-5-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylmorpholine. MS (ESI+) m/z 403.1 (M+H)+.

Workup

  1. extractionthe aqueous phase was extracted with EtOAc (3×)
  2. washwashed with brine (3×)
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by FCC (0-60% EtOAc/heptane)

Sources & evidence

ORD record
ord-12a5cc675d0b4e1e9a7b9d9d38708ca4
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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