(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate

HRID 1396415Notes

Reaction equation

HRID 1396415 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]([NH2:10])=[O:9])=[C:4]([NH:11][C:12]2[N:17]=[C:16]3[CH2:18][CH2:19][CH2:20][C:15]3=[CH:14][CH:13]=2)[CH:3]=1.[NH2:21][C@@H:22]1[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]1[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32]>CN1CCCC1=O>[C:8]([C:5]1[N:6]=[N:7][C:2]([NH:21][C@@H:22]2[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]2[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[CH:3][C:4]=1[NH:11][C:12]1[N:17]=[C:16]2[CH2:18][CH2:19][CH2:20][C:15]2=[CH:14][CH:13]=1)(=[O:9])[NH2:10]

Participants

4

Reactant 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected2×HCID 86689764HCID 86689764, compound

Product 1

HCID 86689765tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamateYield 73.6%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 6-chloro-4-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-ylamino)pyridazine-3-carboxamide (375 mg, 1.29 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (555 mg, 2.59 mmol) in N-methyl-2-pyrrolidinone (3 mL) was treated with tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (555 mg, 2.59 mmol), The reaction mixture was heated at 120° C. for 72 h, then cooled to room temperature, concentrated under high vacuum and the residue obtained was purified by chromatography (spherical silica 20-45 μM, 80 g, Versaflash Supelco, 0 to 5% of a 9:1 MeOH:NH4OH solution in CH2Cl2, 20 min) to give tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (444 mg, 73%) as a light brown foam. 1H NMR (CHLOROFORM-d) δ: 11.30 (s, 1H), 8.19 (s, 1H), 8.06 (d, J=3.4 Hz, 1H), 7.40 (d, J=8.3 Hz, 1H), 6.75-7.10 (m, 1H), 6.61 (d, J=8.3 Hz, 1H), 5.77-6.14 (m, 2H), 3.99 (m, 1H), 3.55-3.74 (m, 1H), 2.67-3.05 (m, 4H), 2.11 (quin, J=7.5 Hz, 2H), 1.18-2.01 (m, 17H); LC-MS 468.2 [M+H]+.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated under high vacuum
  3. customthe residue obtained
  4. customwas purified by chromatography (spherical silica 20-45 μM, 80 g, Versaflash Supelco, 0 to 5% of a 9:1 MeOH:NH4OH solution in CH2Cl2, 20 min)

Sources & evidence

ORD record
ord-d1b7c77f2fbd474fa611feba8b78a214
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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