Dimethyl Sulfoxide → HCID 178496660, compound

HRID 80865Notes

Reaction equation

HRID 80865 reaction equation
[F:1][CH:2]([F:52])[C:3]1[C:7]([CH:8]=O)=[C:6]([N:10]2[CH2:50][CH2:49][C:13]3[N:14]=[C:15]([C:28]4[C:36]([CH3:37])=[CH:35][CH:34]=[C:33]5[C:29]=4[C:30]([CH3:48])=[N:31][N:32]5S(C4C=CC(C)=CC=4)(=O)=O)[N:16]=[C:17]([N:18]4[CH2:23][CH2:22][C@@H:21]([O:24][CH3:25])[C:20]([CH3:27])([CH3:26])[CH2:19]4)[C:12]=3[CH2:11]2)[N:5]([CH3:51])[N:4]=1.Cl.[NH2:54]O.CS(C)=O.C(=O)([O-])[O-].[K+].[K+]>CO>[F:52][CH:2]([F:1])[C:3]1[C:7]([C:8]#[N:54])=[C:6]([N:10]2[CH2:50][CH2:49][C:13]3[N:14]=[C:15]([C:28]4[C:36]([CH3:37])=[CH:35][CH:34]=[C:33]5[C:29]=4[C:30]([CH3:48])=[N:31][NH:32]5)[N:16]=[C:17]([N:18]4[CH2:23][CH2:22][C@@H:21]([O:24][CH3:25])[C:20]([CH3:26])([CH3:27])[CH2:19]4)[C:12]=3[CH2:11]2)[N:5]([CH3:51])[N:4]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 443297Hydroxyamine hydrochlorideHCID 86690296(R)-3-(difluoromethyl)-5-(2-(3,5-dimethyl-1-tosyl-1H-indazol-4-yl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-methyl-1H-pyrazole-4-carbaldehyde

Product 1

HCID 178496660HCID 178496660, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A vessel was charged with (R)-3-(difluoromethyl)-5-(2-(3,5-dimethyl-1-tosyl-1H-indazol-4-yl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-methyl-1H-pyrazole-4-carbaldehyde (54 mg, 0.074 mmol), hydroxylamine hydrochloride (77 mg, 1.105 mmol), and DMSO (491 μL). The vessel was capped and placed in a sand bath preheated to 100° C. and the reaction mixture was stirred at that temperature. After 2 h the mixture was diluted with methanol and transferred to a round-bottomed flask. Potassium carbonate was added, and the mixture stirred for 2 h at 60° C., then allowed to cool to room temperature. The mixture was then filtered through Celite and concentrated, redissolved in methanol, filtered through a syringe filter, and purified by HPLC (15-100% CH3CN in water with 0.1% NH4OH) to provide (R)-3-(difluoromethyl)-5-(2-(3,5-dimethyl-1H-indazol-4-yl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-1-methyl-1H-pyrazole-4-carbonitrile. 1H NMR (400 MHz, CD3OD) δ ppm 7.44 (d, J=8.6 Hz, 1 H), 7.31 (d, J=8.6 Hz, 1 H), 6.54-6.92 (m, 1 H), 4.64 (d, J=14.8 Hz, 1 H), 4.53 (d, J=14.8 Hz, 1 H), 3.85-3.95 (m, 1 H), 3.80 (s, 3 H), 3.67-3.75 (m, 2 H), 3.52 (dd, J=13.4, 1.3 Hz, 1 H), 3.37 (s, 3 H), 3.01-3.10 (m, 4 H), 2.26 (s, 3 H), 2.01 (s, 3 H), 1.97-2.06 (m, 1 H), 1.67-1.79 (m, 1 H), 1.01 (s, 3 H), 0.93 (s, 3 H); MS (ESI+) m/z 576.4 (M+H)+.

Workup

  1. customThe vessel was capped
  2. customplaced in a sand bath
  3. custompreheated to 100° C.
  4. customtransferred to a round-bottomed flask
  5. stirringthe mixture stirred for 2 h at 60° C.
  6. filtrationThe mixture was then filtered through Celite
  7. concentrationconcentrated
  8. dissolutionredissolved in methanol
  9. filtrationfiltered through a syringe
  10. filtrationfilter
  11. custompurified by HPLC (15-100% CH3CN in water with 0.1% NH4OH)

Sources & evidence

ORD record
ord-a8a7125f5d7b436f862362d3ff00b46d
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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