Potassium tert-butoxide → 1-(3-methoxy-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-[(3S,4R)-1-methyl-4-phenylpyrrolidin-3-yl]urea

HRID 588184Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][C:5]2[C:8]([O:11][CH3:12])=[N:9][NH:10][C:4]=2[CH:3]=1.[CH3:13][N:14]1[CH2:18][C@@H:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@H:16]([NH:25][C:26]([NH2:28])=[O:27])[CH2:15]1.CC(C)([O-])C.[K+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1COCC1>[CH3:12][O:11][C:8]1[C:5]2[CH:6]=[N:7][C:2]([NH:28][C:26]([NH:25][C@H:16]3[C@H:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:18][N:14]([CH3:13])[CH2:15]3)=[O:27])=[CH:3][C:4]=2[NH:10][N:9]=1

Participants

Conditions

Temperature: 60 °C

Procedure

6-Chloro-3-methoxy-1H-pyrazolo[4,3-c]pyridine (50 mg, 0.272 mmol), 1-((3S,4R)-1-methyl-4-phenylpyrrolidin-3-yl)urea (Intermediate 17B; 90 mg, 0.409 mmol), BrettPhos pre-catalyst (21.75 mg, 0.027 mmol), and potassium tert-butoxide (1 M in THF, 0.817 mL, 0.817 mmol) were dissolved in THF (1 mL). The vial was degassed with argon for 5 min and the reaction stirred at 60° C. for 16 h. The reaction mixture was filtered through Celite, eluting with MeOH, and the filtrate was concentrated in vacuo while loading onto silica gel. Purification by flash chromatography (0-20% CH2Cl2/MeOH with 1% ammonia) gave 1-(3-methoxy-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-[(3S,4R)-1-methyl-4-phenylpyrrolidin-3-yl]urea. MS ESI calc'd. For C19H22N6O2 [M+1]+ 367. found 367. 1H NMR (500 MHz, DMSO-d6) δ 11.97 (s, 1H), 8.89 (s, 1H), 8.51 (s, 1H), 7.72 (s, 1H), 7.43 (s, 1H), 7.31-7.26 (m, 3H), 7.22-7.18 (m, 2H), 4.22-4.14 (m, 1H), 3.98 (s, 3H), 3.16-3.04 (m, 1H), 2.64-2.58 (m, 2H), 2.48 (s, 3H), 2.38-2.28 (m, 2H).

Workup

customThe vial was degassed with argon for 5 min
filtrationThe reaction mixture was filtered through Celite
washeluting with MeOH
concentrationthe filtrate was concentrated in vacuo
customPurification by flash chromatography (0-20% CH2Cl2/MeOH with 1% ammonia)

Sources & evidence

ORD record: ord-49635f3612514607b12c073d580b3734
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09226922B2

Reaction notes

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