Dimethylcarbamoyl Chloride → Hydrochloric Acid

HRID 1050593Notes

Reaction equation

HRID 1050593 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.[CH3:46][N:47]([CH3:51])[C:48]([Cl:50])=[O:49]>CN1C(=O)CCC1>[C:34]([C:20]1[N:21]=[CH:22][C:23]([N:25]2[CH2:30][CH2:29][CH2:28][C@H:27]3[N:31]([C:48]([N:47]([CH3:51])[CH3:46])=[O:49])[CH2:32][CH2:33][C@@H:26]23)=[N:24][C:19]=1[NH:18][C:15]1[CH:14]=[CH:13][C:12]([CH:9]2[CH2:8][CH2:7][N:6]([CH:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[CH2:11][CH2:10]2)=[CH:17][CH:16]=1)(=[O:35])[NH2:36].[ClH:50]

Participants

6

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 81531DiisopropylethylamineHCID 118114938HCID 118114938, compound

Product 2

HCID 313Hydrochloric AcidYield 1,045.6%HCID 118114657HCID 118114657, 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 dimethylcarbamoyl chloride (62 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 (3aR,7aR)-4-(5-carbamoyl-6-(4-(1-cyclopentylpiperidin-4-yl)phenylamino)pyrazin-2-yl)-N,N-dimethyloctahydro-1H-pyrrolo[3,2-b]pyridine-1-carboxamide (421) as HCl salt (61 mg, 64%). LC-MS (ESI): m/z (M+1) 561.9. UV: λ=267, 275, 304, 334, 372 nm. Proton NMR (CD3OD): δ 7.64 (1H, m), 7.59 (2H, d, J=7.5 Hz), 7.20 (2H, d, J=8.0 Hz), 4.18 (2H, m), 3.71 (3H, m), 3.61-3.56 (2H, m), 3.44 (1H, m), 3.13 (3H, m), 2.90 (7H, s), 2.21 (3H, m), 2.15 (2H, m), 2.07 (1H, m), 1.95 (3H, m), 1.87 (3H, m), 1.73 (4H, m), 1.61 (2H, m) ppm.

Workup

  1. customquenched with 0.5 mL TFA

Sources & evidence

ORD record
ord-6f4e86908d844af1bdda6e0f33faf932
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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