Cyclopropanecarbonyl chloride → Hydrochloric Acid

HRID 1050594Notes

Reaction equation

HRID 1050594 reaction equation
[CH:1]1([N:6]2[CH2:11][CH2:10][CH:9]([C:12]3[CH:17]=[CH:16][C:15]([NH:18][C:19]4[C:20]([C:34]([NH2:36])=[O:35])=[N:21][CH:22]=[C:23]([N:25]5[CH2:30][CH2:29][CH2:28][C@H:27]6[NH:31][CH2:32][CH2:33][C@@H:26]56)[N:24]=4)=[CH:14][CH:13]=3)[CH2:8][CH2:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[CH:46]1([C:49]([Cl:51])=[O:50])[CH2:48][CH2:47]1>CN1C(=O)CCC1>[CH:1]1([N:6]2[CH2:7][CH2:8][CH:9]([C:12]3[CH:13]=[CH:14][C:15]([NH:18][C:19]4[C:20]([C:34]([NH2:36])=[O:35])=[N:21][CH:22]=[C:23]([N:25]5[CH2:30][CH2:29][CH2:28][C@H:27]6[N:31]([C:49]([CH:46]7[CH2:48][CH2:47]7)=[O:50])[CH2:32][CH2:33][C@@H:26]56)[N:24]=4)=[CH:16][CH:17]=3)[CH2:10][CH2:11]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[ClH:51]

Participants

6

Reactant 3

HCID 77637Cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 118114938HCID 118114938, compound

Product 2

HCID 313Hydrochloric AcidYield 994.2%HCID 118114896HCID 118114896, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

3-(4-(1-Cyclopentylpiperidin-4-yl)phenylamino)-5-((3aR,7aR)-dihydro-1H-pyrrolo[3,2-b]pyridin-4(2H,5H,6H,7H,7aH)-yl)pyrazine-2-carboxamide (420) (82 mg, 0.16 mmol) was dissolved in 3 mL NMP. To it were added DIEA (290 μL, 1.68 mmol) and then cyclopropanecarbonyl chloride (61 μL, 0.67 mmol). The mixture was stirred at RT for 2 hours, quenched with 0.5 mL TFA, and subjected to reverse phase prep HPLC using 5 mM HCl (aq) and neat MeCN as mobile phases to isolate 3-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)-5-((3aR,7aR)-1-(cyclopropanecarbonyl)dihydro-1H-pyrrolo[3,2-b]pyridin-4(2H,5H,6H,7H,7aH)-yl)pyrazine-2-carboxamide (422) as HCl salt (58 mg, 62%). LC-MS (ESI): m/z (M+1) 558.8. UV: λ=266, 274, 304, 334, 372 nm.

Workup

  1. customquenched with 0.5 mL TFA

Sources & evidence

ORD record
ord-87ab80f29fcf4634b1ec11c748599f0c
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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