Water → Methyl 1-(4-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-ylcarbamoyl)phenyl)cyclopropanecarboxylate

HRID 1256381Notes

Reaction equation

HRID 1256381 reaction equation
[CH3:1][O:2][C:3]([C:5]1([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=2)[CH2:7][CH2:6]1)=[O:4].C(Cl)(=O)C(Cl)=O.[CH3:23][C:24]1[CH:39]=[C:27]2[N:28]=[C:29]([NH2:38])[CH:30]=[C:31]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[N:26]2[N:25]=1.O>C(Cl)Cl.CN(C=O)C.N1C=CC=CC=1>[CH3:23][C:24]1[CH:39]=[C:27]2[N:28]=[C:29]([NH:38][C:12]([C:11]3[CH:10]=[CH:9][C:8]([C:5]4([C:3]([O:2][CH3:1])=[O:4])[CH2:6][CH2:7]4)=[CH:16][CH:15]=3)=[O:14])[CH:30]=[C:31]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[N:26]2[N:25]=1

Participants

8

Reactant 4

HCID 962WaterHCID 65578Oxalyl chloride2×HCID 58207181HCID 58207181, compoundHCID 588411094-(1-(Methoxycarbonyl)cyclopropyl)benzoic acid

Product 1

HCID 67064610Methyl 1-(4-(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-ylcarbamoyl)phenyl)cyclopropanecarboxylateYield 24.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

4-(1-(Methoxycarbonyl)cyclopropyl)benzoic acid (200 mg, 0.91 mmol) was suspended in CH2Cl2 (5 ml). At 0° C., oxalyl chloride (0.50 ml, 1.0 mmol) was then added, followed by 2 drops of DMF. The mixture was warmed to room temperature. After 2 hours, an additional amount of oxalyl chloride (0.15 ml) was added. After the reaction was completed, 2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-amine (10A, 200 mg, 0.91 mmol) in pyridine (5 ml) was added. After the reaction was complete, water was added and the volatiles were removed in vacuo. The aqueous residue was extracted with EtOAc 3 times. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by preparatory HPLC (65-80% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow powder (96 mg, 24% yield). 1H NMR (400 MHz, DMSO-d6) δ=11.27 (s, 1 H), 8.08-8.04 (m, 2 H), 8.04-7.99 (m, 2 H), 7.96 (s, 1 H), 7.66-7.60 (m, 3 H), 7.52-7.48 (m, 2 H), 6.40 (s, 1 H), 3.57 (s, 3 H), 2.40 (s, 3 H), 1.56-1.50 (m, 2 H), 1.31-1.25 (m, 2 H); ESI-MS: m/z 427.4 (M+H)+.

Workup

  1. customthe volatiles were removed in vacuo
  2. extractionThe aqueous residue was extracted with EtOAc 3 times
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by preparatory HPLC (65-80% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-33357c42bc2b46ca91c8103fd40bc0a7
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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