Tert-Butylamine → Cc-90001

HRID 2201982Notes

Reaction equation

HRID 2201982 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][C@@H:12]([CH3:15])[C@H:11]([OH:16])[CH2:10]2)[C:5]([C:17]([NH2:19])=[O:18])=[CH:4][N:3]=1.[C:20]([NH2:24])([CH3:23])([CH3:22])[CH3:21]>CS(C)=O>[C:20]([NH:24][C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][C@@H:12]([CH3:15])[C@H:11]([OH:16])[CH2:10]2)[C:5]([C:17]([NH2:19])=[O:18])=[CH:4][N:3]=1)([CH3:23])([CH3:22])[CH3:21]

Participants

4

Reactant 2

HCID 6385Tert-ButylamineHCID 1182537882-chloro-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino) pyrimidine-5-carboxamide

Product 1

HCID 71237511Cc-90001

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
68 °C

Procedure

To a reactor was charged 2-chloro-4-{[(1R,3R,4R)-3-hydroxy-4-methylcyclohexyl]amino}pyrimidine-5-carboxamide (41 kg), t-butylamine (105.3 kg) and DMSO (205 L). The batch was heated to 68° C. under 10 psig of nitrogen pressure, held for 80 h, and cooled to 25° C. The batch was filtered through a 0.45 μm in-line filter to a second reactor. The batch was heated to 60° C., and water (205 L) was charged through a 0.45 μm in-line filter. The batch was seeded with micronized Compound 1 (820 g) agitated at 60° C. for over an hour, and water (615 L) was charged to the batch through a 0.45 μm in-line filter in 3 h at 60° C. The batch was agitated for 1 h at 60° C., cooled to 25° C. over 6 h, filtered, and washed with water (410 mL), which was filtered through a 0.45 μm in-line filter. The solids were dried in a vacuum oven at 40° C. with nitrogen bleed for over 72 h to give 2-(tert-butylamino)-4-{[(1R,3R,4R)-3-hydroxy-4-methylcyclohexyl]amino}pyrimidine-5-carboxamide as Form A and a white solid (43.5 kg, 94% yield). 1H NMR (DMSO-d6) δ 0.95 (d, J=6.2 Hz, 3H), 0.97-1.28 (m, 4H), 1.37 (s, 9H), 1.60-1.75 (m, 1H), 1.83-2.00 (m, IH), 2.06-2.26 (m, 1H), 2.86-3.07 (m, 1H), 3.74-4.01 (m, 1H), 4.59 (d, J=5.7 Hz, 1H), 6.65 (br. s., 1H), 7.03 (br. s., 1H), 7.57 (br. s., 1H), 8.36 (s, 1H), 8.93 (br. s., 1H).

Workup

  1. temperaturecooled to 25° C
  2. filtrationThe batch was filtered through a 0.45 μm
  3. filtrationin-line filter to a second reactor
  4. temperatureThe batch was heated to 60° C.
  5. additionwater (205 L) was charged through a 0.45 μm
  6. filtrationin-line filter
  7. additionwas charged to the batch through a 0.45 μm
  8. filtrationin-line filter in 3 h at 60° C
  9. stirringThe batch was agitated for 1 h at 60° C.
  10. temperaturecooled to 25° C. over 6 h
  11. filtrationfiltered
  12. washwashed with water (410 mL), which
  13. filtrationwas filtered through a 0.45 μm
  14. filtrationin-line filter
  15. customThe solids were dried in a vacuum oven at 40° C. with nitrogen
  16. custombleed for over 72 h

Sources & evidence

ORD record
ord-586541f334c7406ea0517c87b258fbb9
Source dataset
uspto-grants-2016_06
Patent number
US09365524B2

Reaction notes

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