Hydrochloric Acid → HCID 58169282, compound

HRID 1484873Notes

Reaction equation

HRID 1484873 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:15](N)=[CH:14][N:13]=[C:12]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=4)[N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1.[ClH:23].N([O-])=O.[Na+].CC1C=CC(COC(NNC(C2C=NC=CN=2)=O)=O)=CC=1.C([O-])([O-])=O.[Na+].[Na+]>Cl[Cu]>[Cl:23][C:15]1[C:10]([NH:9][C:6]2[CH:5]=[C:4]([CH:1]3[CH2:3][CH2:2]3)[NH:8][N:7]=2)=[N:11][C:12]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)=[N:13][CH:14]=1

Participants

7

Reactant 5

HCID 313Hydrochloric Acid2×HCID 10340Sodium CarbonateHCID 478568p-tolylmethyl N-(pyrazine-2-carbonylamino)carbamateHCID 23668193Sodium NitriteHCID 58169570HCID 58169570, compound

Product 1

HCID 58169282HCID 58169282, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 62652Cuprous chlorideCatalyst

Procedure

To N4-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(pyridin-2-yl)pyrimidine-4,5-diamine (0.88 g, 0.003 mmol, 1 equiv.) in conc.HCl (3 mL) at ice-bath was added NaNO2 (0.23 g, 0.0033 mmol, 1.1 equiv.). After 1 h, CuCl (0.33 g, 0.0033 mmol, 1.1 equiv.) in conc.HCl (6 mL) was added at 0° C. After 30 min, the reaction mixture was allowed to stand at room temperature for further 3 h, poured into ice water and adjusted to pH10 with Na2CO3, extracted with EA (50 mL×3). The organic phase was combined, dried (Na2SO4), purified with silicon chromatography (EA: PE=2:1) to produce 5-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(pyridin-2-yl)pyrimidin-4-amine (Compound 182) (0.47 g, 50%). LC-MS (m/z)=313 [M+H]+; 1H NMR (400 MHz, DMSO-d6): δ 0.75-0.78 (m, 2H), 0.97-1.02 (m, 2H), 1.96-2.02 (m, 1H), 6.44-6.45 (m, 1H), 7.92-7.93 (m, 1H), 8.44 (s, 2H), 8.73 (d, J=2.8 Hz, 1H), 8.87 (d, J=3.6 Hz, 1H), 10.20 (bs, 1H)

Workup

  1. waitAfter 30 min
  2. waitto stand at room temperature for further 3 h
  3. extractionextracted with EA (50 mL×3)
  4. dry with materialdried (Na2SO4)
  5. custompurified with silicon chromatography (EA: PE=2:1)

Sources & evidence

ORD record
ord-968836f5352245c7bf10c8116170cd9e
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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