tert-Butyl [1-(aminomethyl)cyclopropyl]carbamate → methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((1-(tert-butoxycarbonylamino)cyclopropyl)methylamino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate

HRID 85553

Reaction equation

HRID 85553 reaction equation
N([C@:4]12[CH2:39][CH2:38][C@@H:37]([C:40]([CH3:42])=[CH2:41])[C@@H:5]1[C@@H:6]1[C@@:19]([CH3:22])([CH2:20][CH2:21]2)[C@@:18]2([CH3:23])[C@@H:9]([C@:10]3([CH3:36])[C@@H:15]([CH2:16][CH2:17]2)[C:14]([CH3:25])([CH3:24])[C:13]([C:26]2[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][CH:27]=2)=[CH:12][CH2:11]3)[CH2:8][CH2:7]1)=C=O.[NH2:43][CH2:44][C:45]1([NH:48][C:49](=[O:55])[O:50][C:51]([CH3:54])([CH3:53])[CH3:52])[CH2:47][CH2:46]1>C1COCC1>[C:51]([O:50][C:49]([NH:48][C:45]1([CH2:44][NH:43][C@:4]23[CH2:39][CH2:38][C@@H:37]([C:40]([CH3:42])=[CH2:41])[C@@H:5]2[C@@H:6]2[C@@:19]([CH3:22])([CH2:20][CH2:21]3)[C@@:18]3([CH3:23])[C@@H:9]([C@:10]4([CH3:36])[C@@H:15]([CH2:16][CH2:17]3)[C:14]([CH3:25])([CH3:24])[C:13]([C:26]3[CH:27]=[CH:28][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:34][CH:35]=3)=[CH:12][CH2:11]4)[CH2:8][CH2:7]2)[CH2:46][CH2:47]1)=[O:55])([CH3:52])([CH3:54])[CH3:53]

Participants

4

Reactant 2

HCID 46864104tert-Butyl [1-(aminomethyl)cyclopropyl]carbamateHCID 86676572methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-isocyanato-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate

Product 1

HCID 89400527methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((1-(tert-butoxycarbonylamino)cyclopropyl)methylamino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoateYield 66.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-isocyanato-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate (600 mg, 1.053 mmol) and N,N-diisopropyethyllamine (0.734 mL, 4.21 mmol) in THF (6 mL) was added tert-butyl 1-(aminomethyl)cyclopropylcarbamate (294 mg, 1.579 mmol). The resulting mixture was stirred at rt. After 16 h, the solvent was concentrated. The crude material was dissolved in THF (1 mL) and MeOH (2 mL), filtered and purified by reverse phase preparative HPLC (method 1) to give the title compound (499.5 mg, 58% yield) as a white solid. LCMS: m/e 756.7 (M+H)+, 2.75 min (method 7). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.0 (2H, d, J=8.5 Hz), 7.2 (2H, d, J=8.5 Hz), 5.3-5.3 (1H, m), 5.1 (1H, br. s.), 4.8 (1H, s), 4.7 (1H, s), 3.9 (3H, s), 3.5-3.5 (1H, m), 3.4 (1H, d, J=14.3 Hz), 2.8 (1H, br. s.), 2.6 (1H, d, J=12.8 Hz), 2.4 (1H, dd, J=12.2, 8.2 Hz), 2.1 (1H, dd, J=17.4, 6.4 Hz), 1.9-2.1 (2H, m), 1.8 (1H, d, J=13.4 Hz), 1.7-1.8 (1H, m), 1.7 (3H, s), 1.7-1.7 (2H, m), 1.5-1.7 (3H, m), 1.5 (9H, s), 1.4-1.5 (5H, m), 1.2-1.3 (1H, m), 1.1-1.2 (2H, m), 1.1 (3H, s), 1.0 (3H, s), 1.0 (3H, s), 0.9 (6H, s), 0.8-0.9 (3H, m). 13C NMR (CHLOROFORM-d) δ ppm 14.1, 15.4, 16.1, 19.0, 19.5, 20.7, 20.8, 24.8, 27.0, 28.1, 29.1, 29.2, 29.4, 31.4, 33.2, 35.1, 36.0, 36.6, 37.2, 40.4, 41.4, 41.6, 46.0, 49.1, 49.6, 51.7, 52.5, 77.3, 80.1, 109.9, 123.7, 127.6, 128.2, 129.8, 146.0, 148.4, 149.2, 167.0.

Workup

  1. concentrationthe solvent was concentrated
  2. dissolutionThe crude material was dissolved in THF (1 mL)
  3. filtrationMeOH (2 mL), filtered
  4. custompurified by reverse phase preparative HPLC (method 1)

Sources & evidence

ORD record
ord-376d3c6d78eb41b1aef14a26aeebfa8f
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Linked notes

Loading…