(1S,2S)-2-phenylcyclopropane-1-carbonyl chloride → (1S,2S)-N-(2-Methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-yl)-2-phenylcyclopropanecarboxamide

HRID 1256419Notes

Reaction equation

HRID 1256419 reaction equation
[C:1]1([C@H:7]2[CH2:9][C@@H:8]2[C:10](Cl)=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:13][C:14]1[CH:29]=[C:17]2[N:18]=[C:19]([NH2:28])[CH:20]=[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:16]2[N:15]=1>N1C=CC=CC=1>[CH3:13][C:14]1[CH:29]=[C:17]2[N:18]=[C:19]([NH:28][C:10]([C@H:8]3[CH2:9][C@@H:7]3[C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[O:11])[CH:20]=[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:16]2[N:15]=1

Participants

4

Reactant 2

HCID 7005116(1S,2S)-2-phenylcyclopropane-1-carbonyl chlorideHCID 58207181HCID 58207181, compound

Product 1

HCID 67064526(1S,2S)-N-(2-Methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-yl)-2-phenylcyclopropanecarboxamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

In a round-bottomed flask was (1S,2S)-2-phenylcyclopropanecarbonyl chloride (161 mg, 0.892 mmol) added in Pyridine (3 mL) to give a yellow suspension. 2-methyl-7-phenylpyrazolo[1,5-a]pyrimidin-5-amine (10A, 100 mg, 0.446 mmol) was added portionwise at 0° C. The temperature was slowly raised to room temperature. The reaction was quenched with saturated sodium bicarbonate and partitioned between ethyl acetate and water. The separated organic layer was dried over Mg2SO4, filtered, and concentrated under reduced pressure (3×100 mL). The reaction mixture was filtered and purified by preparatory HPLC (70-80% MeCN/H2O gradient+0.01% TFA). Received 46 mg (28%) of yellow solid. 1H NMR (DMSO-d6) δ: 11.28 (s, 1H), 7.94-8.06 (m, 2H), 7.90 (s, 1H), 7.52-7.68 (m, 3H), 7.27-7.35 (m, 2H), 7.16-7.26 (m, 3H), 6.33 (s, 1H), 2.42-2.49 (m, 1H), 2.28-2.43 (m, 4H), 1.50-1.57 (m, 1H), 1.44 (ddd, J=8.1, 6.5, 4.0 Hz, 1H); [α]D20=+294° (c=0.6060, MeOH). ESI-MS: m/z 369.0 (M+H)+.

Workup

  1. customIn a round-bottomed flask was
  2. customto give a yellow suspension
  3. customThe reaction was quenched with saturated sodium bicarbonate
  4. custompartitioned between ethyl acetate and water
  5. dry with materialThe separated organic layer was dried over Mg2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure (3×100 mL)
  8. filtrationThe reaction mixture was filtered
  9. custompurified by preparatory HPLC (70-80% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-b48a6e2dbab14b73aae1c790b763e803
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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