Dichloromethane → 7-Methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carboxylic acid cinnolin-3-ylmethyl-((S)-1-cyclobutyl-pyrrolidin-2-ylmethyl)-amide

HRID 2220724Notes

Reaction equation

HRID 2220724 reaction equation
C(O[C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][N:14]([CH2:30][C:31]1[N:32]=[N:33][C:34]2[C:39]([CH:40]=1)=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:15]([C:17]1[CH:27]=[C:26]([O:28][CH3:29])[C:20]2[O:21][C:22]([CH3:25])([CH3:24])[O:23][C:19]=2[CH:18]=1)=[O:16])=O)(C)(C)C.FC(F)(F)C(O)=O.ClCCl.ClCCl.[C:54]1(=O)[CH2:57]C[CH2:55]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[N:33]1[C:34]2[C:39](=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:40]=[C:31]([CH2:30][N:14]([CH2:13][C@@H:9]2[CH2:10][CH2:11][CH2:12][N:8]2[CH:6]2[CH2:57][CH2:54][CH2:55]2)[C:15]([C:17]2[CH:27]=[C:26]([O:28][CH3:29])[C:20]3[O:21][C:22]([CH3:25])([CH3:24])[O:23][C:19]=3[CH:18]=2)=[O:16])[N:32]=1

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 14496CyclobutanoneHCID 5049666Sodium triacetoxyborohydrideHCID 21863450Trifluoroacetic acid methylene chlorideHCID 58622200(S)-2-{[Cinnolin-3-ylmethyl-(7-methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carbonyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 586221927-Methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carboxylic acid cinnolin-3-ylmethyl-((S)-1-cyclobutyl-pyrrolidin-2-ylmethyl)-amide

Procedure

Experimental conditions analogous to Example 1, from 172 mg (0.31 mmol) of (S)-2-{[cinnolin-3-ylmethyl-(7-methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carbonyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester and 3 mL 10% trifluoroacetic acid/dichloromethane. The crude deprotected material was submitted to reductive amination reaction in 5 mL dichloromethane using 108 mg (1.55 mmol) of cyclobutanone and 329 mg (1.55 mmol) sodium triacetoxyborohydride. The reaction mixture was purified using flash chromatography elution with 0-10% methanol in dichloromethane, gave 47 mg of pale yellow solid as the free base. LC-MSD, m/z for C29H34N4O4 [M+H]+: 503.7. 1H NMR (400 MHz, CDCl3): δ 1.6-2.5 (m, 16 H), 2.8-2.9 (m, 1 H), 3.5-3.8 (m, 3 H), 3.8 (s, 3 H), 3.9-4.0 (m, 2 H), 5.1-5.3 (m, 2 H), 6.8 (bs, 1 H), 7.2 (bs, 1 H), 7.7-7.9 (m, 4 H), 8.4-8.5 (m, 1 H).

Workup

  1. customThe reaction mixture was purified
  2. washflash chromatography elution with 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-49d5d8d2de5243b7adf98c9a0a8b3302
Source dataset
uspto-grants-2008_08
Patent number
US07417062B2

Reaction notes

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