Sodium Carbonate → (R)-4-(6-(3-cyclopropyl-1-ethyl-1H-pyrazol-5-yl)-2-(3,5-dimethyl-1-tosyl-1H-indazol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylmorpholine

HRID 80861Notes

Reaction equation

HRID 80861 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][C@H:23]2[CH3:28])[C:5]2[CH2:11][N:10]([C:12]3[N:16]([CH2:17][CH3:18])[N:15]=[C:14]([CH:19]4[CH2:21][CH2:20]4)[CH:13]=3)[CH2:9][CH2:8][C:6]=2[N:7]=1.[CH3:29][C:30]1[C:38]2[C:33](=[CH:34][CH:35]=[C:36]([CH3:48])[C:37]=2B2OC(C)(C)C(C)(C)O2)[N:32]([S:49]([C:52]2[CH:58]=[CH:57][C:55]([CH3:56])=[CH:54][CH:53]=2)(=[O:51])=[O:50])[N:31]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:19]1([C:14]2[CH:13]=[C:12]([N:10]3[CH2:9][CH2:8][C:6]4[N:7]=[C:2]([C:37]5[C:36]([CH3:48])=[CH:35][CH:34]=[C:33]6[C:38]=5[C:30]([CH3:29])=[N:31][N:32]6[S:49]([C:52]5[CH:58]=[CH:57][C:55]([CH3:56])=[CH:54][CH:53]=5)(=[O:50])=[O:51])[N:3]=[C:4]([N:22]5[CH2:27][CH2:26][O:25][CH2:24][C@H:23]5[CH3:28])[C:5]=4[CH2:11]3)[N:16]([CH2:17][CH3:18])[N:15]=2)[CH2:21][CH2:20]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 71240658HCID 71240658, compoundHCID 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

Product 1

HCID 71240671(R)-4-(6-(3-cyclopropyl-1-ethyl-1H-pyrazol-5-yl)-2-(3,5-dimethyl-1-tosyl-1H-indazol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylmorpholine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of (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 (0.116 g, 0.288 mmol) in DME (1.4 mL) was added 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indazole (0.129 g, 0.302 mmol), Pd(Ph3P)4 (0.033 g, 0.029 mmol) and aqueous Na2CO3 (0.43 mL, 2 M). The mixture was sparged with argon and heated in a microwave reactor at 130° C. for 1 h 20 min. The mixture was filtered and concentrated under reduced pressure. Purification by FCC (40-100% EtOAc/heptane) provided the title compound (R)-4-(6-(3-cyclopropyl-1-ethyl-1H-pyrazol-5-yl)-2-(3,5-dimethyl-1-tosyl-1H-indazol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylmorpholine. MS (ESI+) m/z 667.2 (M+H)+.

Workup

  1. customThe mixture was sparged with argon
  2. filtrationThe mixture was filtered
  3. concentrationconcentrated under reduced pressure
  4. customPurification by FCC (40-100% EtOAc/heptane)

Sources & evidence

ORD record
ord-c8d9b63c97a54f7aa8a68b42d7e876d7
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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