Potassium Carbonate → HCID 86697449, compound

HRID 1478283Notes

Reaction equation

HRID 1478283 reaction equation
[NH2:1][C@@H:2]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:3]([N:5]([C@H:7]1[CH2:11][CH2:10][N:9]([C:12]2[CH:17]=[CH:16][N:15]3[N:18]=[CH:19][C:20](Br)=[C:14]3[N:13]=2)[CH2:8]1)[CH3:6])=[O:4].[CH3:26][O:27][C:28]1[C:33](B(O)O)=[CH:32][CH:31]=[CH:30][N:29]=1.C(=O)([O-])[O-].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C(#N)C.CC([O-])=O.CC([O-])=O.[Pd+2].O>[NH2:1][C@@H:2]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:3]([N:5]([C@H:7]1[CH2:11][CH2:10][N:9]([C:12]2[CH:17]=[CH:16][N:15]3[N:18]=[CH:19][C:20]([C:33]4[C:28]([O:27][CH3:26])=[N:29][CH:30]=[CH:31][CH:32]=4)=[C:14]3[N:13]=2)[CH2:8]1)[CH3:6])=[O:4]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 2762709(2-Methoxypyridin-3-yl)boronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86697447HCID 86697447, compound

Product 1

HCID 86697449HCID 86697449, compoundYield 17.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

(S)-2-amino-N—((S)-1-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-3-yl)-N,4-dimethylpentanamide (220 mg, 0.54 mmol), 2-methoxypyridine-3-boronic acid (164 mg, 1.1 mmol), potassium carbonate (291 mg, 2.15 mmol), Pd(OAc)2 (2 mg, 0.011 mmol) and x-phos (10 mg, 0.022 mmol) were taken up in 2 mL acetonitrile and 1 mL water and heated in a sealed tube at 85° C. for 2 hours. Reaction was then filtered through celite with acetonitrile and DCM reduced in vacuo, then purified on Shimadzu neutral phase prep and product fractions lyophilized to get (S)-2-amino-N—((S)-1-(3-(2-methoxypyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-3-yl)-N,4-dimethylpentanamide 41.3 mg as 0.5 eq formic salt. 1H NMR (400 MHz, DMSO-d6) δ 8.87-8.97 (m, 1H), 8.72 (s, 1H), 8.50 (s, 1H), 8.30 (s, 1H), 7.96 (dd, J=2.02, 4.80 Hz, 1H), 7.00-7.11 (m, 1H), 6.51 (d, J=7.83 Hz, 1H), 4.00 (s, 3H), 3.48-3.64 (m, 1H), 3.43 (br. s., 3H), 2.96 (s, 2H), 2.81 (s, 1H), 2.11-2.28 (m, 2H), 1.72-1.89 (m, 1H), 1.19-1.39 (m, 2H), 0.90 (dd, J=1.89, 6.69 Hz, 6H). (ESI) m/z 438 [(M+H)]+, calc'd for C23H31N7O2: 437.5.

Workup

  1. customReaction
  2. filtrationwas then filtered through celite with acetonitrile and DCM
  3. custompurified on Shimadzu neutral phase prep and product fractions

Sources & evidence

ORD record
ord-e20451d429a34e8fbd18af5ddbdc100b
Source dataset
uspto-grants-2016_08
Patent number
US09403832B2

Reaction notes

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